Home / Deep Research / adrenoleukodystrophy

adrenoleukodystrophy

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of adrenoleukodystrophy. Core disease mechanisms, molecular and cellular path...

2026-04-14
Asta MONDO:0018544 Model: Asta Scientific Corpus Retrieval 20 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of adrenoleukodystrophy. Core disease mechanisms, molecular and cellular path...

This report is retrieval-only and is generated directly from Asta results.

  • Papers retrieved: 20
  • Snippets retrieved: 20

Relevant Papers

[1] Modeling and rescue of defective blood–brain barrier function of induced brain microvascular endothelial cells from childhood cerebral adrenoleukodystrophy patients

  • Authors: Catherine A. A. Lee, Hannah S. Seo, A. Armién, F. Bates, J. Tolar et al.
  • Year: 2018
  • Venue: Fluids and Barriers of the CNS
  • URL: https://www.semanticscholar.org/paper/0f5c432624d4ad49cfed766a22b6e9101d975e1f
  • DOI: 10.1186/s12987-018-0094-5
  • PMID: 29615068
  • PMCID: 5883398
  • Citations: 40
  • Summary: The finding that BBB integrity is decreased in X-linked adrenoleukodystrophy patients and can be rescued with block copolymers opens the door for the discovery of BBB-specific molecular markers that can indicate the onset of ccALD and has therapeutic implications for preventing the conversion.
  • Evidence snippets:
  • Snippet 1 (score: 0.474) > The molecular mechanisms responsible for the onset and progression of childhood cerebral adrenoleukodystrophy (ccALD) remain poorly understood. ccALD is one form of X-linked adrenoleukodystrophy (X-ALD), an inherited metabolic storage disorder affecting 1 in 17,000 individuals [1]. X-ALD is caused by mutations in the ABCD1 gene which codes for the ABCD1 protein [2]. ABCD1 is a peroxisomal transporter protein responsible for transporting very long-chain fatty acids (VLCFAs) from the cytosol into the peroxisome for subsequent beta-oxidation [3,4]. Mutation type and location are not predictive of phenotype, as the same ABCD1 mutation can lead to clinically distinct phenotypes [5][6][7][8][9]. A more frequent and less severe phenotype, adrenomyeloneuropathy (AMN), presents with demyelination in the long tracts of the spinal cord and progressive axonopathy, usually around the third or fourth decade of life. Heterozygous females will develop similar symptoms by age 60 [10][11][12]. ccALD, the most rapidly progressing phenotype, occurs in boys ages 2-12 and is characterized by sudden inflammatory demyelination in the brain and death within a few years [13,14]. ccALD affects about 40% of males with an ABCD1 mutation [15,16]. MRI observation of gadolinium enhancement in the brain remains the only method to detect this progression [17][18][19][20][21]. Infections or head trauma have been described as initiators of the conversion from AMN to ccALD, but typically no extrinsic factor can be identified [22][23][24]. Current treatment for ccALD includes hematopoietic cell transplant (HCT), but this must be performed at the earliest stages of the disease [12,14,25,26]. > Much attention has focused on VLCFAs in the search for alternative treatments.

[2] Human Dermal Fibroblast: A Promising Cellular Model to Study Biological Mechanisms of Major Depression and Antidepressant Drug Response

  • Authors: P. Mesdom, R. Colle, É. Lebigot, S. Trabado, Eric Deflesselle et al.
  • Year: 2020
  • Venue: Current Neuropharmacology
  • URL: https://www.semanticscholar.org/paper/79368e365458486de96794333613c12a6063bf54
  • DOI: 10.2174/1570159X17666191021141057
  • PMID: 31631822
  • PMCID: 7327943
  • Citations: 12
  • Summary: This review highlights the great and still underused potential of HDF, which stands out as a very promising tool in the understanding of MDD and AD mechanisms of action.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > Background: Human dermal fibroblasts (HDF) can be used as a cellular model relatively easily and without genetic engineering. Therefore, HDF represent an interesting tool to study several human diseases including psychiatric disorders. Despite major depressive disorder (MDD) being the second cause of disability in the world, the efficacy of antidepressant drug (AD) treatment is not sufficient and the underlying mechanisms of MDD and the mechanisms of action of AD are poorly understood. Objective The aim of this review is to highlight the potential of HDF in the study of cellular mechanisms involved in MDD pathophysiology and in the action of AD response. Methods The first part is a systematic review following PRISMA guidelines on the use of HDF in MDD research. The second part reports the mechanisms and molecules both present in HDF and relevant regarding MDD pathophysiology and AD mechanisms of action. Results HDFs from MDD patients have been investigated in a relatively small number of works and most of them focused on the adrenergic pathway and metabolism-related gene expression as compared to HDF from healthy controls. The second part listed an important number of papers demonstrating the presence of many molecular processes in HDF, involved in MDD and AD mechanisms of action. Conclusion The imbalance in the number of papers between the two parts highlights the great and still underused potential of HDF, which stands out as a very promising tool in our understanding of MDD and AD mechanisms of action

[3] A Journey through Huntington's Disease: Exploring Genetics, Neurobiology, and Therapeutic Advances

  • Authors: Sandeep Dey, Shreyas Katta, S. Suresh, Janhvi Mishra
  • Year: 2024
  • Venue: International Journal For Multidisciplinary Research
  • URL: https://www.semanticscholar.org/paper/735574648bec278cf15dc25fd5f1d735afaf6ae6
  • DOI: 10.36948/ijfmr.2024.v06i03.19194
  • Summary: The clinical features, ethics, and neurobiology of HD are discussed and the exciting approaches being employed today to advance understanding of underlying mechanisms in an effort to develop therapies that would delay the onset and slow progression of this disease are reviewed.
  • Evidence snippets:
  • Snippet 1 (score: 0.445) > Also, we present a modern view on the molecular biology of HD as a representative of the group of polyglutamine diseases, with an emphasis on conformational changes of mutant huntingtin, disturbances in its cellular processing, and proteolytic stress in degenerating neurons. > The main pathogenetic mechanisms of neurodegeneration in HD are discussed in detail, such as autophagy, impaired mitochondrial biogenesis, lysosomal dysfunction, organelle and protein transport, inflammation, oxidative stress, and transcription factor modulation. However, other unravelling mechanisms are still unknown. This practical and brief review summarises some of the currently known functions of the wild-type huntingtin protein and the recent findings related to the mechanisms involved in HD pathogenesis. Cellular mechanisms implicated in HD pathogenesis: The major mechanisms associated with HD pathogenesis are depicted here. The schematic shows a presynaptic neuron and a postsynaptic neuron flanked by two astrocytes. Huntingtin gene(HTT) itself is depicted as a "solenoid," based on the presumed folding due to its HEAT repeats. The mechanisms depicted are multimerization of mHtt-containing complexes, transcriptional modulation, ER-Golgi stress pathways, mitochondria and energy homeostasis, microtubular dynamics, endocytic and vesicular trafficking dynamics, autophagy, and synaptic signalling mechanisms. mHTT(mutant HTT protein). Traditionally, therapeutic approaches to HD have included compounds developed for psychiatric indications based on the affected neuronal circuitry: the frontal and motor corticostriatal circuits. None of these were initially developed for the treatment of HD. In this review we focus on the cellular and biological pathways affected by mutant HTT (mHTT) and the current status of associated drug discovery efforts. We also emphasise the need for further clinical research to validate existing hypotheses, which are mostly derived from animal studies and postmortem human tissues. It is generally accepted that most candidate therapeutics fail due to lack of efficacy in pivotal clinical studies.

[4] Biomarker Identification, Safety, and Efficacy of High-Dose Antioxidants for Adrenomyeloneuropathy: a Phase II Pilot Study

  • Authors: C. Casasnovas, M. Ruiz, A. Schlüter, A. Naudí, S. Fourcade et al.
  • Year: 2019
  • Venue: Neurotherapeutics
  • URL: https://www.semanticscholar.org/paper/58ebde4f86151c0fa04ddc9d0df6ee2b13cc24ea
  • DOI: 10.1007/s13311-019-00735-2
  • PMID: 31077039
  • PMCID: 6985062
  • Citations: 41
  • Influential citations: 1
  • Summary: A positive signal is suggested for extending these studies to phase III randomized, placebo-controlled, longer-term trials with the actual identified dose, and candidate biomarkers that may serve for patient stratification and disease progression, which merit replication in future clinical trials are suggested.
  • Evidence snippets:
  • Snippet 1 (score: 0.441) > X-Adrenoleukodystrophy (X-ALD) is the most frequently inherited leukodystrophy, with a minimum incidence of 1 in 14,700 live births [1]. The gene mutated in the disease (ABCD1) encodes the ALD protein (ALDP), a peroxisomal transporter that imports very long-chain fatty acids (VLCFA) into the peroxisome for degradation [2,3]. Elevated plasma VLCFA is a pathognomonic biomarker for this disorder, although it lacks predictive value for disease severity or progression [4]. Different phenotypes have been described in X-ALD. Virtually all patients who reach adulthood develop the most frequent phenotype, adrenomyeloneuropathy (AMN), in their third and fourth decades of life. The initial symptoms are limited to the spinal cord and peripheral nerves. Patients develop progressive spastic paraparesis, sensory ataxia with impaired vibration sense, sphincter dysfunction, pain in the legs, and impotence [5]. Neurophysiological findings reveal axonal neuropathy and disturbances in evoked potentials [6]. Brain magnetic resonance imaging (MRI) results are often abnormal, mainly affecting the corticospinal tract [7]. Approximately 80% of patients suffer from adrenocortical insufficiency [5]. Women carriers often present mild myelopathy after the fourth decade of life [8]. The most severe disease phenotype, cerebral childhood adrenoleukodystrophy (cALD), presents rapidly progressive inflammatory brain demyelination with a lethal outcome unless diagnosed early and treated with hematopoietic bone marrow transplant [9] or the new available hematopoietic stem cell therapy [10]. > At present, there is no satisfactory treatment for patients with AMN [11]. Oxidative stress is a major factor driving X-ALD pathogenesis [12][13][14][15][16][17] and appears very early in life [12].

[5] Pain Study in X-Linked Adrenoleukodystrophy in Males and Females

  • Authors: V. Bachiocco, M. Cappa, A. Petroni, E. Salsano, C. Bizzarri et al.
  • Year: 2021
  • Venue: Pain and Therapy
  • URL: https://www.semanticscholar.org/paper/32acab0b52b16acea6ab44581f0bf426e9872a2e
  • DOI: 10.1007/s40122-021-00245-0
  • PMID: 33609269
  • PMCID: 8119579
  • Citations: 5
  • Summary: The study of pain and of the sensory profile appears to indicate a difference in the mechanisms underlying the AMN/cAMN/ cALD and AD clinical forms and in the treatment of the respective generated pain types.
  • Evidence snippets:
  • Snippet 1 (score: 0.441) > Adrenoleukodystrophy (ALD) is an X-linked inherited metabolic disease caused by mutations in the ATP-binding cassette (ABC) transporter subfamily D member 1 gene (ABCD1) which encodes for a peroxisomal transmembrane protein involved in the transport of very long chain fatty acids (VLCFA) from cytosol into peroxisomes, where they undergo b-oxidation [1,2]. Abnormal accumulation of VLCFA is ubiquitous, but the nervous system, adrenal cortex and testis are mainly affected [1,3]. The excess of VLCFA and the development of molecular and metabolic alterations cause different functional impairment in the tissues, and the downstream mechanisms dictating the signature and severity of the disease are still largely unclear [4][5][6][7]. The clinical phenotype is heterogeneous, although three major variants have been described. Addison's disease only (AD) is characterized by decreased cortisol production and release, and thus by adrenal insufficiency [8,9]. Adrenomyeloneuropathy (AMN) involves a progressive axonopathy affecting sensory ascending and motor descending spinal tracts as well as peripheral nerves, which causes sensory and motor disturbances [5,6,8]. Cerebral adrenoleukodystrophy (cALD), or cerebral adrenomyeloneuropathy (cAMN), is marked by myelin destabilization and serious neuroinflammation [1,5,6,8], giving rise to severe cognitive, behavioral and neurological dysfunctions. Sixty-six percent of AMN patients present adrenal involvement [8], while 35% [10,11] progress towards an overt cerebral inflammatory form. > Signs and symptoms of the disease have been described in males and also in females, so-called carriers. Nevertheless, depending on the studies, 50% or more of such women present some neurological anomaly, 57% manifest a peripheral neuropathy and 63% develop a late progressive myelopathy [12,13]. Both large and small nerve fiber dysfunction has been described in AMN-like females [8,14] and in AMN males [15][16][17].

[6] Mitochondrial Dysfunction in Diabetes: Shedding Light on a Widespread Oversight

  • Authors: F. Iheagwam, A. J. Joseph, E. D. Adedoyin, Olawumi Toyin Iheagwam, Samuel Akpoyowvare Ejoh
  • Year: 2025
  • Venue: Pathophysiology
  • URL: https://www.semanticscholar.org/paper/dbf8042761c1a5fc50f8cd894cc498505abac7cb
  • DOI: 10.3390/pathophysiology32010009
  • PMID: 39982365
  • PMCID: 12077258
  • Citations: 25
  • Summary: This review aims to elucidate the complex link between mitochondrial dysfunction and diabetes, covering the spectrum of diabetes types, the role of mitochondria in insulin resistance, highlighting pathophysiological mechanisms, mitochondrial DNA damage, and altered mitochondrial biogenesis and dynamics.
  • Evidence snippets:
  • Snippet 1 (score: 0.436) > The landscape of DM research is continuously evolving, with emerging technologies and approaches offering new insights into the pathophysiology of the disease and potential therapeutic targets. Advancements in omics technologies, encompassing genomes, transcriptomics, proteomics, and metabolomics, have transformed the molecular mechanisms underlying DM [134]. High-throughput sequencing techniques enable comprehensive analysis of genetic variants, gene expression profiles, protein abundance, and metabolite levels associated with DM and its complications [135]. Single-cell omics approaches provide unprecedented resolution and granularity, allowing researchers to dissect cellular heterogeneity and identify novel cell types, subpopulations, and signalling pathways involved in DM pathogenesis. Integrating multi-omics data sets offers a systems-level perspective of DM, unravelling complex networks of molecular interactions and regulatory circuits underlying disease progression [136]. > In addition to omics technologies, advances in imaging modalities, such as MRI, PET, and optical imaging, enable non-invasive visualisation and quantification of metabolic, functional, and structural changes. Molecular imaging probes targeting specific biomarkers and metabolic pathways provide valuable insights into disease mechanisms and treatment responses in preclinical and clinical settings [85]. Despite significant progress in DM research, numerous unanswered questions and knowledge gaps persist, hindering the ability to develop effective prevention and treatment strategies. Key areas requiring further investigation include the role of epigenetics, environmental factors, and the microbiome in DM susceptibility and progression. Moreover, the interaction between environmental cues and genetic predisposition remains incompletely understood, highlighting the need for comprehensive multi-omics studies and large-scale epidemiological analyses to identify gene-environment interactions and modifiable risk factors for DM [137]. Furthermore, the heterogeneity of DM phenotypes and clinical outcomes poses a challenge for personalised medicine approaches, necessitating robust biomarkers and predictive models to stratify patients based on disease subtypes, prognosis, and treatment response [138].

[7] Exome sequencing and metabolomic analysis of a chronic kidney disease and hearing loss patient family revealed RMND1 mutation induced sphingolipid metabolism defects

  • Authors: Nagwa Gaboon, B. Banaganapalli, K. Nasser, M. Razeeth, Mosab S. Alsaedi et al.
  • Year: 2019
  • Venue: Saudi Journal of Biological Sciences
  • URL: https://www.semanticscholar.org/paper/f1f1341fd61e31f39a5129e7c80ff67cd0b6fb0f
  • DOI: 10.1016/j.sjbs.2019.10.001
  • PMID: 31889854
  • PMCID: 6933272
  • Citations: 17
  • Influential citations: 1
  • Summary: Genetic defects in RMND1 gene alters the mitochondrial energy metabolism leading to the accumulation of ceramide, and subsequently promote dysregulated apoptosis and tissue necrosis in kidneys, this study suggests.
  • Evidence snippets:
  • Snippet 1 (score: 0.430) > One of the recently identified nuclear genes involved in mitochondrial respiratory chain deficiencies is RMND1 (Required for Meiotic Nuclear Division protein 1) (Garcia-Diaz et al., 2012;Janer et al., 2012). It has been demonstrated that various novel and common recessive mutations in RMND1 are associated with multiple phenotypes characterized by delayed maturation of vision, developmental delay, dilated cardiomyopathy, deafness and neurological defects (Gupta et al., 2016), renal tubular acidosis type 4 presented as hyponatraemia and hyperkalaemia and cystic/hypoplastic kidneys (Ng et al., 2016). Likewise, complex clinical spectrum of patients with RMND1 mutations is emerging with infantile encephalomyopathy with lactic acidosis (Garcia-Diaz et al., 2012;Casey et al., 2016) to a less severe form of developmental delay, hypotonia, renal disease and congenital sensorineural deafness (Janer et al., 2015). Therefore, molecular screening of RMND1 gene will help identify the inheritance mode of causative genetic mutations in patients with renal and or neurological defects. > MIDs have complex etiologies with underlying cross talk of inter and intra molecular signaling. Hence, metabolomic studies on these patients could provide a better understanding of the interconnectivity between genetic and molecular networks (Davies, 2018). Metabolomic profiling examines the metabolic changes in body fluids driven from cellular processes to understand the onset and pathogenesis of disease phenotype (Abbiss et al., 2019). Metabolomics analyzes metabolites by either targeted or untargeted approaches. The untargeted approach involves hypothesis free surveying of hundreds of thousands of small molecule metabolites for discovering novel mechanisms or pathways, whereas the targeted one refers to measuring predefined sets of metabolites, typically focusing on a few pathways of interest (Kalim and Rhee, 2017). The specific relationship between inherited mutations in mitochondrial proteins and their functional impacts in terms of metabolic defects in chronic kidney disease (CKD) is not yet well characterized.

[8] Intensity of MRI Gadolinium Enhancement in Cerebral Adrenoleukodystrophy: A Biomarker for Inflammation and Predictor of Outcome following Transplantation in Higher Risk Patients

  • Authors: W. Miller, L. F. Mantovani, J. Muzic, J. Rykken, R. Gawande et al.
  • Year: 2016
  • Venue: American Journal of Neuroradiology
  • URL: https://www.semanticscholar.org/paper/f6a2042d09199bf0e5695cf8cf8edccbe3a01e20
  • DOI: 10.3174/ajnr.A4500
  • PMID: 26427835
  • Citations: 36
  • Influential citations: 1
  • Summary: Gadolinium enhancement intensity on brain MR imaging can be scored simply and reproducibly for cerebral adrenoleukodystrophy and in boys with higher risk cerebral disease, the enhancement score itself predicts neurologic outcome following treatment.
  • Evidence snippets:
  • Snippet 1 (score: 0.430) > order affecting approximately 1 in 21,000 males. Mediated by elevated concentrations of very long chain fatty acids, the disease may manifest as central nervous system demyelination, primary hypoadrenalism, and/or primary hypogonadism. The disease results from pathogenic mutations in the peroxisomal transporter ABCD1 gene, but genotype does not predict the presentation, and different presentations may occur within the same family. 1, 2 In 35% of affected males, cerebral involvement (cerebral adrenoleukodystrophy [cALD]) begins in childhood. This devastating phenotype is characterized by rapidly progressive central nervous demyelination and, if untreated, usually death within years of onset of clinical signs and symptoms. 3 Postmortem analyses of affected brains have implicated mononuclear inflammatory mechanisms. [4][5][6] Radiographic changes generally precede clinical neurologic disease by several years in childhood cALD and are characterized by symmetric, expanding white matter lesions. 7 Consistent with known neuroinflammatory histopathology, gadolinium enhancement is typically observed near the leading edge of active demyelination and, when present, strongly predicts dis-ease progression. 8,9 The cALD brain MR imaging severity scale of Loes et al 10 is commonly used to quantify radiographic disease burden in adrenoleukodystrophy. Increasing Loes scores denote accumulating white matter disease and atrophy in defined neuroanatomic or functional regions: periventricular/subcortical areas (parieto-occipital, anterior-temporal, and frontal), corpus callosum, visual and auditory pathways, frontopontine-corticospinal projection fibers (internal capsule and brain stem), basal ganglia, cerebellum, and anterior thalamus. For patients with ALD with no cerebral involvement, the Loes score is by definition zero, while maximal cerebral involvement on the scale (Loes ϭ 34) correlates with profound neurologic impairment. 10 Although experimental gene therapy trials are currently underway, allogeneic hematopoietic stem cell transplantation (HSCT) remains the standard therapy to arrest cerebral disease progression in cALD

[9] Clinical metabolomics in type 2 diabetes mellitus: from pathogenesis to biomarkers

  • Authors: Chuanxin Liu, Hetao Chen, Yujin Ma, Lei Zhang, Lulu Chen et al.
  • Year: 2025
  • Venue: Frontiers in Endocrinology
  • URL: https://www.semanticscholar.org/paper/36f8d26a208b7b96763df2e9aa3211e440031c0e
  • DOI: 10.3389/fendo.2025.1501305
  • PMID: 40070584
  • PMCID: 11893406
  • Citations: 11
  • Summary: The results facilitate understanding the pathophysiology and mechanism of type 2 diabetes mellitus and supports research in accurate diagnosis, risk prediction, curative effect, distinct stages, and prognosis judgment of T2DM.
  • Evidence snippets:
  • Snippet 1 (score: 0.430) > T2DM is a chronic disease characterized by two primary pathophysiological mechanisms: ① a reduction in the mass and function of pancreatic b cells, ranging from 20% to 65%, which leads to impaired insulin secretion; ② insulin resistance, where cells in muscles, fat, and liver tissues fail to respond adequately to insulin (9). Consequently, higher levels of insulin are required to maintain normal blood glucose concentrations by inhibiting hepatic glucose production and promoting glucose uptake in muscle and adipose tissues. Prolonged exposure to elevated levels of circulating insulin leads to the development of insulin resistance in peripheral tissues, and over time, the pancreas fails to produce sufficient insulin to overcome this cellular resistance (10). However, due to the long latent period and absence of obvious symptoms initially, reversing T2DM with drug intervention is difficult after the symptoms are exposed or clinically confirmed in light of clear diagnostic criteria. According to the literature, the pathogenesis and process of metabolic syndromes such as diabetes and its complications are mainly reflected in the metabolite network, and the mechanism changes at the gene level are also found in the network. Studies have shown that some related metabolites in patients with diabetes have changed before the occurrence of obvious organic damage (11). Therefore, it is necessary to scientifically prevent T2DM in the early stages of disease onset. Fortunately, clinical metabolomics were employed to understand the progression pathologies of T2DM and its corresponding complications in detail (12). Studies have demonstrated that metabolomic analysis enables the exploration of metabolic disorders associated with T2DM, thereby deepening our understanding of disease progression (13,14). This approach has the potential to facilitate novel clinical diagnoses and the development of effective treatment strategies. Moreover, identifying specific metabolites may provide promising biomarkers for the early prediction, prevention, and management of hyperglycemia and its complications (15). In recent years, excellent progress has been made in the study of T2DM and its complications through High throughput sequencing method, i.e., a discipline specifically focused on metabolic small molecules. > Clinical metabolomics is a type of systems biology research closely linked to phenotype.

[10] IPSC-Derived Astrocytes to Model Neuroinflammatory and Metabolic Responses in X-linked Adrenoleukodystrophy.

  • Authors: P. Parasar, N. Kaur, J. Singh
  • Year: 2023
  • Venue: Journal of biotechnology and biomedicine
  • URL: https://www.semanticscholar.org/paper/6fab52a715449279623a980a8025e71b8298d32a
  • DOI: 10.26502/jbb.2642-91280091
  • PMID: 38077449
  • Citations: 7
  • Summary: X-linked adrenoleukodystrophy (X-ALD) is an inherited metabolic disorder caused by pathogenic variants in the ABCD1 gene, leading to accumulation of saturated very long chain fatty acids (VLCFA) in body fluids and tissues including brain and spinal cord. In the absence of a clear genotype-phenotype correlation the molecular mechanisms of the fatal cerebral adrenoleukodystrophy (cALD) and the milder adrenomyeloneuropathy (AMN) phenotypes remain unknown. Given our previous evidence of role of a...
  • Evidence snippets:
  • Snippet 1 (score: 0.423) > X-linked adrenoleukodystrophy (X-ALD) is a progressive peroxisomal disease due to a defective ABCD1 gene encoding the peroxisomal ABC half-transporter ABCD1 or adrenoleukodystrophy (ALD) protein. ABCD1 mutations impair β-oxidation of fatty acids, leading to accumulation of very long chain fatty acids (VLCFAs), predominantly C26:0 in blood and tissues, which adversely affects the brain, spinal cord, and adrenals [1]. A total of 1000 unique variants of ABCD1 in >3400 cases ABCD1 variants have been reported in X-ALD; however, no correlation of genotype to clinical phenotype exists (https://adrenoleukodystrophy.info/) [2]. X-ALD phenotypes include rapidly progressive inflammatory demyelinating cerebral adrenoleukodystrophy (cALD), milder adult-onset forms, adrenomyeloneuropathy (AMN. Approximately 35% of affected males develop cALD before reaching 12 years of age. Without early intervention, most patients with cALD die within a decade after diagnosis. AMN is a gradually developing phenotype, first affecting males with dysfunctional ABCD1 at age 20-30 years manifesting with gait disturbances and bladder dysfunction. About 30% of patients with AMN develop cerebral inflammation, ultimately progressing to the fatal cALD form in adulthood [1,2]. Human astrocytes are the major cell population in the central nervous system and play a substantial role in X-ALD pathogenesis, and the peroxisomal ABCD1 protein plays a role in the murine astrocyte inflammatory response [3]. We previously documented that loss of adenosine monophosphate-activated protein kinase α1 (AMPKα1) in patients with cALD was associated with a higher inflammatory profile in patient-derived cells [4][5][6]; however, the underlying definitive mechanisms of phenotypic variability and differential inflammatory responses between AMN and cALD phenotypes remain unknown.

[11] Omics Data and Their Integrative Analysis to Support Stratified Medicine in Neurodegenerative Diseases

  • Authors: Valentina La Cognata, Giovanna Morello, S. Cavallaro
  • Year: 2021
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/fd3586b07f23e89cece5c7ea2abc6fddd871568e
  • DOI: 10.3390/ijms22094820
  • PMID: 34062930
  • PMCID: 8125201
  • Citations: 35
  • Summary: How omics technologies and their integration have provided new insights into the molecular heterogeneity underlying the most prevalent NDs, aiding to define early diagnosis and progression markers as well as therapeutic targets that can translate into stratified treatment approaches are discussed, bringing us closer to the goal of personalized medicine in neurology.
  • Evidence snippets:
  • Snippet 1 (score: 0.421) > Neurodegenerative diseases (NDs) are debilitating and largely untreatable conditions characterized by a decline of nervous system functions due to a progressive neuronal loss in the brain and spinal cord. The classification of NDs is still usually based on the clinical presentation (i.e., cognitive decline, speech difficulties and motor impairment), anatomical regions and cell types affected [1,2]. As the exact molecular mechanisms of the disease pathogenesis and progression remain unclear, the clinical management of NDs is limited to simply mitigating neurodegeneration and relieving symptoms rather than reversing the damage done [1,3,4]. > NDs can be either monogenic, like Huntington disease, or complex, highly heterogeneous-including Alzheimer's disease (AD), Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS)-and characterized by variable molecular phenotypes, progression courses or patterns of neuro-biochemical markers of brain damage, making patient counseling, disease management and pharmaceutical care particularly difficult [3]. The underlying mechanisms of these complex NDs are polyfactorial and depend on the combination of genetic, biological and environmental factors. The presence of abnormal protein conformations, excessive immune response and inflammation, impaired nucleocytoplasmic transport, mitochondrial dysfunction, neuronal dysfunction and autophagy are common features of neurodegeneration [5,6]. However, despite considerable efforts, the molecular mechanisms involved in the complex phenotype of NDs are still largely unknown, and current treatments cannot prevent the development of the disease. The failure of the majority of neurological clinical trials, especially during Phase 3, can be attributed to a lack of efficacy, probably due to the incorrect selection of the target population [7,8]. A full readout of ND conditions to support stratified medicine. From the genome onwards, information gathered from all omics molecular layers of NDs conditions will aid researchers and clinicians to better characterize the disease's molecular heterogeneity, stratify patients by novel biomarkers and improve therapeutic outcomes.

[12] Changes in Serum Proteomic Profiles at Different Stages of Pregnancy Toxemia in Goats

  • Authors: M. Uzti̇mür, C. N. Ünal, Gurler Akpinar
  • Year: 2025
  • Venue: Journal of Veterinary Internal Medicine
  • URL: https://www.semanticscholar.org/paper/4b9c488b5dbd65d7b26fd2ad9aed70e8c4b59942
  • DOI: 10.1111/jvim.70139
  • PMID: 40492724
  • PMCID: 12150350
  • Summary: Understanding the serum proteome profiles of goats with pregnancy toxemia might help identify the proteomes and pathways responsible for the development of this disease and improve diagnosis and treatment.
  • Evidence snippets:
  • Snippet 1 (score: 0.417) > The pathophysiology and progression of this disease are not fully understood. > Traditional biomedical research has focused on the analysis of single genes, proteins, metabolites, or metabolic pathways in diseases. This molecular reductionist approach is based on the assumption that identifying genetic variations and molecular components will lead to new treatments for diseases [13][14][15][16]. However, many diseases are complex and multifactorial, and in order to determine the phenotype of such diseases, it is necessary to understand the changes that occur in more than one gene, pathway, protein, or metabolite at the cellular, tissue, and organismal levels [17][18][19]. Therefore, in recent years, proteomics, as one field of multi-omics technologies, has helped in evaluating the complex pathogenetic mechanisms of different diseases from a broad perspective and has made substantial contributions [20,21]. In veterinary medicine, proteomic analysis of metabolic diseases such as ketosis [16], hypocalcemia [22], and fatty liver [23] in dairy cows has contributed valuable insights for the definition of new pathophysiological pathways and new diagnosis and treatment protocols for these diseases. The proteomic approach can contribute importantly to a broad and detailed understanding of the changes that occur at the organismal level associated with the increase in BHBA concentration in goats with pregnancy toxemia. Our aim was to evaluate the serum protein profiles of goats with SPT or CPT using proteomic techniques to determine the proteomic profiles of these animals and to identify the relevant pathophysiological mechanisms.

[13] 18O-assisted dynamic metabolomics for individualized diagnostics and treatment of human diseases

  • Authors: E. Nemutlu, Song Zhang, N. Juranic, A. Terzic, S. Macura et al.
  • Year: 2012
  • Venue: Croatian Medical Journal
  • URL: https://www.semanticscholar.org/paper/880f053c7f060db4b990e447d0a22c4b69372ddb
  • DOI: 10.3325/cmj.2012.53.529
  • PMID: 23275318
  • PMCID: 3541579
  • Citations: 28
  • Summary: The potential use of dynamic phosphometabolomic platform for disease diagnostics currently under development at Mayo Clinic is described and discussed briefly.
  • Evidence snippets:
  • Snippet 1 (score: 0.417) > Living cells represent an integrated and interacting network of genes, transcripts, proteins, small signaling molecules, and metabolites that define cellular phenotype and function. Traditionally the focus of biomedical research was on individual genes, single protein targets, single metabolites, and metabolic or signaling pathways. This "molecular reductionist" paradigm was based on the assumption that identifying genetic variations and molecular components would lead to discovery of cures for human diseases. However, most of diseases are complex and multi-factorial and the disease phenotype is determined by the alterations of multiple genes, pathways, proteins and metabolites (at cellular, tissue, and organismal levels). Therefore, an integrated "omics" approach is more viable direction for uncovering alterations in metabolic networks, disease mechanisms, and mechanisms of drug effects. > Recent advent of large-scale metabolomics and fluxomic (metabolite dynamics and metabolic flux analysis) completed the "omics revolution" (Figure 1), where genomics, transcriptomics, proteomics, metabolomics, and fluxomics all together complement phenotype determination of living organism. Such integrated "omics" cascades provide a framework for advances in system and network biology, integrative physiology, and system medicine as well as system pharmacology and regenerative medicine. Noteworthy is the "reverse omic" approach or "metabolomicsinformed pharmacogenomics, " where discovery of specific metabolite changes have led to discovery of genetic alterations (2). Therefore, bringing new "omics" technologies to clinical practice will improve disease diagnostics and treatment by targeting drugs and procedures for each unique transcriptomic and metabolomic profiles.

[14] Psychobiotics at the Frontiers of Neurodegenerative and Neuropsychiatric Research

  • Authors: Guillermo Roberto Jiménez-Pareyón, J. Cristóbal-Luna, Y. García-Martínez, Cynthia Garfias-Noguez, Morayma Ramírez-Damián et al.
  • Year: 2025
  • Venue: Microorganisms
  • URL: https://www.semanticscholar.org/paper/6c92b8101905064ff4e4e8585f4fa86ebfac0826
  • DOI: 10.3390/microorganisms13122718
  • PMID: 41471921
  • PMCID: 12735313
  • Summary: A review of current evidence on the GBA’s involvement in conditions such as Alzheimer’s disease, Parkinson’s disease, depression, and anxiety examines how psychobiotics may modulate neuroinflammation, oxidative stress, and neurotransmitter signaling, thereby contributing to cognitive and emotional regulation.
  • Evidence snippets:
  • Snippet 1 (score: 0.416) > Neurodegenerative diseases (NDs) are a group of disorders characterized by the progressive deterioration of the central or peripheral nervous system. These diseases cause morphological changes in the brain, leading to significant cognitive or motor impairments, debilitating symptoms, and a reduced quality of life [16]. NDs involve complex cellular responses triggered by the accumulation of pathologically altered brain substances, ultimately resulting in irreversible loss of neuronal populations [17]. > The pathophysiology of NDs is multifactorial and intricate, involving cellular, molecular, and genetic mechanisms. These include protein misfolding and aggregation, oxidative stress, mitochondrial dysfunction, cytoskeletal abnormalities, disrupted synaptic networks, neuronal death, aberrant cell proliferation, neuroinflammation, demyelination, altered axonal transport, dysregulated energy metabolism, and abnormal modifications of DNA or RNA [16,[18][19][20][21][22]. > NDs can be classified according to several criteria, such as their etiology, the molecular mechanisms involved, and the anatomical regions affected [23]. Although multiple classification systems exist, these disorders often share overlapping cellular and molecular mechanisms [24], which complicates efforts to categorize them into a single scheme. From a mechanistic perspective, NDs commonly exhibit recurring pathological events such as neuroinflammation, oxidative stress, mitochondrial dysfunction, and the accumulation of misfolded proteins [16]. Recent classification systems increasingly emphasize the type of protein aggregates for diagnostic accuracy [25]. Clinically, NDs can also be classified clinically based on predominant symptoms, such as movement disorders in PD and Huntington's disease, cognitive deficits in AD, or a combination of both [12,26,27]. This approach allows for a better understanding of their heterogeneity and facilitates the development of more specific therapeutic strategies. Among the spectrum of neurodegenerative conditions, AD and PD are the most prevalent and extensively studied (Figure 1).

[15] Crosstalk of organelles in Parkinson’s disease – MiT family transcription factors as central players in signaling pathways connecting mitochondria and lysosomes

  • Authors: M. Lang, P. Pramstaller, I. Pichler
  • Year: 2022
  • Venue: Molecular Neurodegeneration
  • URL: https://www.semanticscholar.org/paper/61554668ad754c9cf8ea032cfb48773e91592041
  • DOI: 10.1186/s13024-022-00555-7
  • PMID: 35842725
  • PMCID: 9288732
  • Citations: 20
  • Summary: The activation of MiT transcription factors through genetic and pharmacological approaches have shown encouraging results at ameliorating PD-related phenotypes in in vitro and in vivo models and focus on the role of the MiT pathway and its potential as pharmacological target against PD.
  • Evidence snippets:
  • Snippet 1 (score: 0.414) > PD is a NDD that is characterized by pathological protein misfolding and aggregation as well as organellar dysfunction leading to neuronal cell death, which causes motor-and non-motor symptoms. Mitochondrial homeostasis and quality control have historically been recognized as crucial contributors to PD pathogenesis, and several aspects of mitochondrial biology are impaired in PD patients and models. In addition, defects of macroautophagy and the ALP have been observed in cell and animal models of PD as well as PD patients' brains, where constitutive autophagy is indispensable for adaptation to stress and energy deficiency. Various mechanisms are involved in the interplay between PD-related mitochondrial defects, lysosomal dysfunctions, and protein aggregate formations. The specific disease cascade in PD patients may differ based on which genetic and environmental factors act as main triggers. As outlined in this review, the functions of various organellar compartments are tightly linked and influence each other. Connections between these organelles are constituted among others by mitophagy, metabolite homeostasis, organellar dynamics, including exo-and endocytosis, and cellular signaling cascades, including Ca 2+ signaling, This may lead to the recognition of druggable proteins that can influence MiT activation and help to develop pharmacologically relevant molecules that would increase lysosomal biogenesis and boost degradation pathways in the brain of affected individuals. Such treatment strategies would best be applied before debilitating effects of the disease are being experienced. This, however, will require parallel efforts for the development of early diagnostic methods that would help to recognize biological malfunctions before the damage to cells is too extensive and clinical symptoms appear. Only if diseasealtering treatment options are applied before significant brain regions are impacted by the disease, it will be possible to achieve truly meaningful effects. Overall, more work will be needed to bridge basic knowledge of the main pathways affecting PD with their potential clinical applications, but recent developments in the field have uncovered promising pathways, including the here described approaches, that may provide disease-altering therapies against PD.

[16] Common immunopathogenesis of central nervous system diseases: the protein-homeostasis-system hypothesis

  • Authors: Kyung-Yil Lee
  • Year: 2022
  • Venue: Cell & Bioscience
  • URL: https://www.semanticscholar.org/paper/2984270ae67451b93007040848d9694d19714c9f
  • DOI: 10.1186/s13578-022-00920-5
  • PMID: 36384812
  • PMCID: 9668226
  • Citations: 9
  • Influential citations: 1
  • Summary: This article proposes a common immunopathogenesis of CNS diseases, including prion diseases, Alzheimer’s disease, and genetic diseases, through the PHS hypothesis, which proposes that the immune systems in the host control those substances according to the size and biochemical properties of the substances.
  • Evidence snippets:
  • Snippet 1 (score: 0.411) > There are hundreds of genetic diseases of the CNS. The defective proteins in genetic disorders include structural proteins for neurotransmitter receptors and other receptors or ion channels on CNS cells, and proteins involved in enzymatic process, metabolism (transport), or signal transduction pathways in various communication systems [98]. Because a discussion of each genetic disease is beyond the scope of this review, only crucial points about the pathogenesis of genetic diseases are discussed. Singlegene defect diseases of the CNS can be caused by a defective product from a gene, i.e., a protein deficiency or a malfunctioning protein. In general, autosomal dominant genetic diseases are caused by structural protein defects, and autosomal recessive diseases are caused by defects in enzymatic proteins. However, certain genetic diseases that involve an enzymatic or multifunctional protein defect can induce structural cell injury during the natural course of the illness. > Patients with genetic diseases, including HD, familial JCD, GSS, and the genetic forms of AD and PD, show different clinical manifestations from other affected people in their family, including the time of onset of neurological symptoms, speed of progression of the disease, and prognosis, suggesting that phenotypes can vary even when the genotypes are identical. Likewise, similar phenotypes of CNS symptoms can be found in different genetic diseases. In genetic animal models, the phenotypes of single gene knockout can vary by strain in mice, and the clinical manifestations of a gene defect can differ between mice and humans, and mice null for some genes have also no observable phenotypic abnormalities compared with controls [99]. These findings suggest that default of a protein might be at least partly controlled by individual's control systems and that there might exist a similar immune/repair system against cell injury in genetic diseases. > The pathophysiology of most genetic diseases in the CNS is complex because any affected gene is associated with numerous proteins and their corresponding activations of genes and epigenetic changes that occur during disease processes. Thus, the use of a genetic marker for diagnosing or predicting a prognosis remains impractical in clinical settings [100].

[17] Potential cerebrospinal fluid metabolomic biomarkers and early prediction model for Parkinson’s disease

  • Authors: Yifan Zhang, Yuexin Yan, Xiangxu Kong, Haijun Zhang, Shengyuan Su
  • Year: 2025
  • Venue: Frontiers in Aging Neuroscience
  • URL: https://www.semanticscholar.org/paper/57fa4686dec3091fc3019e6771a6d0db010c8e23
  • DOI: 10.3389/fnagi.2025.1582362
  • PMID: 40520532
  • PMCID: 12163037
  • Summary: The differential expression of CSF metabolites reveals early cellular metabolic changes, providing insights for early diagnosis and monitoring PD progression, and shows a bidirectional causal relationship exists between genetically determined PD susceptibility and metabolites.
  • Evidence snippets:
  • Snippet 1 (score: 0.409) > Cerebrospinal fluid (CSF), which directly interacts with brain cells, offers an accurate reflection of the underlying molecular mechanisms of PD. While the α-synuclein seed amplification assay in CSF demonstrates high sensitivity and specificity, it reflects only part of the disease pathology, highlighting the need for additional biomarkers to fully characterize PD (Postuma and Berg, 2016). CSF metabolomics, through the mapping and quantification of various small-molecule metabolites, provides a comprehensive insight into cellular metabolism and neurotransmitter alterations (Stoessel et al., 2018). With recent advancements in liquid chromatography-mass spectrometry (LC-MS/ MS), key biomarkers related to lipid metabolism, polyamines, amino acids, and purine metabolism have garnered increasing attention (Trezzi et al., 2017;Kremer et al., 2021). > This study aims to explore the differences in various metabolites, particularly lipid metabolites, at different clinical stages of PD (including healthy controls, prodromal PD, and clinically diagnosed PD patients) using CSF metabolomics as a data-driven source. The study further aims to predict the risk of PD progression. The objectives of this study are as follows: (1) to identify cerebrospinal metabolic biomarkers at different stages of PD progression; (2) to assess the reliability of predictive models by developing a clinical risk model for PD; (3) to link lipid metabolism biomarkers with clinical manifestations to provide clinical utility; (4) to uncover potential mechanisms underlying PD progression through metabolic biomarkers and associated molecular pathways; (5) MR analysis was conducted using publicly available genome-wide association data to evaluate the causal relationship between differential metabolites and Parkinson's disease.

[18] Evolution of adrenoleukodystrophy model systems

  • Authors: R. Montoro, V. Heine, S. Kemp, M. Engelen
  • Year: 2020
  • Venue: Journal of Inherited Metabolic Disease
  • URL: https://www.semanticscholar.org/paper/f56613d587d84a989445ee01f3a8911ac13192e5
  • DOI: 10.1002/jimd.12357
  • PMID: 33373044
  • PMCID: 8248356
  • Citations: 7
  • Summary: An overview of the different ALD modeling strategies from single‐celled to multicellular organisms and from in vitro to in vivo approaches is provided, and how emerging iPSC‐derived technologies could improve the understanding of this highly complex disorder is introduced.
  • Evidence snippets:
  • Snippet 1 (score: 0.409) > X-linked adrenoleukodystrophy (ALD; OMIM: 300100) is the most common peroxisomal neurometabolic disorder characterized by a spectrum of symptoms and defined by mutations in the ABCD1 gene. 1 Nearly all men and ~80% of women develop slowly progressive spinal cord disease known as adrenomyeloneuropathy (AMN). In men, features range from adrenal insufficiency to progressive inflammatory cerebral demyelination (cerebral ALD), which are very rare findings among women with ALD. 1,2 oreover, given that monozygotic twins can have a disconcordant disease course, a combination of rare genetic modifiers, epigenetic, and environmental factors have been hypothesized to impact the disease outcome. 3,4 he complex clinical presentation and the absence of a genotype-phenotype correlation are complicating our understanding of the disease. > Model systems have been extensively employed in an attempt to understand the pathophysiology of ALD (Table 1). Truncation of the ABCD1 gene has been the most used strategy to experimentally model ALD. in vitro studies provided us the majority of knowledge on ABCD1 biochemistry and function, but obviously come with limitations when trying to understand a neurological dysfunction. In addition, the creation of animal knockout models of the human ABCD1 ortholog has advanced our insights into disease mechanisms. However, animal models also failed to fully recapitulate the complex neurodegenerative etiology of ALD. Recently, the ALD field has begun to explore the potentials of induced pluripotent stem cell (iPSC)-based modeling approaches. The first patient iPSC studies presented biochemical hallmarks of ALD in disease-relevant cell types of the nervous system. 5,6 ach model system recapitulates certain aspects of the disorder. This exposes the complexity of ALD and therefore the challenge to create a comprehensive model system to fully understand ALD. In this review, we provide an overview of the different ALD modeling strategies from single-celled to multicellular organisms and from in vitro to in vivo approaches, and introduce how emerging iPSC-derived technologies could improve the understanding of this disorder.

[19] Chitotriosidase as a biomarker of cerebral adrenoleukodystrophy

  • Authors: Paul J. Orchard, Troy C. Lund, Wes P. Miller, Steven M. Rothman, Gerald V. Raymond et al.
  • Year: 2011
  • Venue: Journal of Neuroinflammation
  • URL: https://www.semanticscholar.org/paper/4421d817f113af080aef7f8216acdf0980f46597
  • DOI: 10.1186/1742-2094-8-144
  • PMID: 22014002
  • PMCID: 3236018
  • Citations: 24
  • Influential citations: 2
  • Summary: Elevation of chitotriosidase activity in patients with active C-ALD is confirmed and these levels predict prognosis of patients with C-ALD undergoing transplantation, suggesting that these levels predict prognosis of patients with C-ALD undergoing transplantation.
  • Evidence snippets:
  • Snippet 1 (score: 0.406) > Adrenoleukodystrophy (ALD) is an X-linked, peroxisomal disorder of very long chain fatty acid (VLCFA) metabolism, resulting in the accumulation of VLCFA in the adrenal gland, testes and brain. The disease frequency is approximately 1 in 17,000 males, and has been reported to be similar in distribution across ethnic and racial groups [1,2]. The capacity to metabolize VLCFA, a reaction that normally takes place in the peroxisome, is impaired in patients with X-ALD due to defects in the ABCD1 gene encoding a peroxisomal membrane protein designated ALDp. A large number of genetic mutations have been identified as causing disease, and there is substantial clinical variability within kindreds despite a conserved genotype [2,3]. > The most severe phenotype of ALD is the cerebral form (C-ALD), which is observed in approximately 40% of children affected by ALD. The median age of clinical onset is 7 years. A characteristic finding associated with C-ALD is inflammation of the white matter of the brain, with changes suggesting active oxidative damage thought to be due to the inflammatory process [4]. The disease is associated with progressive demyelination, and once initiated, generally leads to a vegetative state or death within several years of onset. The only available therapy shown to provide long-term stabilization of C-ALD is allogeneic hematopoietic stem cell transplantation, although there is an interest in the development of gene therapy [5]. At this time, the mechanism by which transplantation arrests the disease process is incompletely understood. It is thought to be due, at least in part, to modulation of the neuroinflammatory process. Given the risks associated with transplantation, the current standard of care for neurologically asymptomatic patients is to monitor them prospectively for cerebral involvement by scheduled MRI imaging. If white matter changes with gadolinium enhancement are observed, providing evidence of active inflammation and progression, transplantation should be expediently performed. > Currently, there is no clear means of determining which patients with ALD are likely to develop C-ALD. In addition, for patients with symptoma

[20] ABCD2 Is a Direct Target of β-Catenin and TCF-4: Implications for X-Linked Adrenoleukodystrophy Therapy

  • Authors: Chul-Yong Park, H. Kim, Jiho Jang, Hyunji Lee, Jae Souk Lee et al.
  • Year: 2013
  • Venue: PLoS ONE
  • URL: https://www.semanticscholar.org/paper/4e8884c5bcd9270af9e657b160a20a22e7d39ca0
  • DOI: 10.1371/journal.pone.0056242
  • PMID: 23437103
  • PMCID: 3578850
  • Citations: 17
  • Summary: Results demonstrate for the first time the direct regulation of ABCD2 by β-catenin and TCF-4 in X-linked adrenoleukodystrophy.
  • Evidence snippets:
  • Snippet 1 (score: 0.404) > X-linked adrenoleukodystrophy (X-ALD) is the most common peroxisomal disorder and is caused by mutations or large deletions of one or more exons in the ABCD1 gene located in Xq28, which encodes the peroxisomal member of the ATP-binding cassette (ABC) transporter subfamily D member 1 (ABCD1), also known as adrenoleukodystrophy protein (ALDP) [1,2]. X-ALD has an incidence of 1 in 17,000 males, and has several clinical phenotypes, namely severe childhood cerebral form (CCALD, early-onset type), a slowly progressive form called adrenomyeloneuropathy (AMN, late-onset type), and adult cerebral form (ACALD) [3,4]. Currently, no therapeutic drugs for X-ALD are available, although gene correction of autologous hematopoietic stem cell with a wild-type version of the ABCD1 gene by a lentiviral vector has been shown to provide clinical benefit in X-ALD patients [5]. ABCD1 transports very long chain fatty acids (VLCFAs; those with more than 22 carbon atoms) or their CoA derivatives across the peroxisomal membrane for b-oxidation. Recently, it was demonstrated that human ABCD1 was able to transport VLCFA-CoA into the peroxisome in a yeast system [6]. Dysfunction of ABCD1 results in increased levels of saturated (C24:0 and C26:0) and monounsaturated (C26:1) VLCFAs in the plasma and tissues of X-ALD patients, due to the reduced boxidation of VLCFAs in peroxisomes [7]. Recently, we first reported the generation of X-ALD patient-derived induced pluripotent stem (iPS) cell models [8]. Generated X-ALD iPS cells were successfully differentiated into oligodendrocytes, the main cell type affected by the disease, and notably revealed the underlying pathophysiology which had not been observed in patients' fibroblasts or animal models.

Notes

  • This provider combines search_papers_by_relevance with snippet_search.
  • No synthesis or second-stage model call is performed.