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Neuromyelitis Optica

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

2026-05-08
Asta MONDO:0019100 Model: Asta Scientific Corpus Retrieval 20 citations

Asta Literature Retrieval: Pathophysiology and clinical mechanisms of Neuromyelitis Optica. 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] Unraveling the Immunopathogenesis of Multiple Sclerosis: The Dynamic Dance of Plasmablasts and Pathogenic T Cells

  • Authors: Y. Matsuzaka, R. Yashiro
  • Year: 2023
  • Venue: Biologics
  • URL: https://www.semanticscholar.org/paper/a560fba99a3b87c378dd7e6027dda1a80de312d6
  • DOI: 10.3390/biologics3030013
  • Citations: 1
  • Influential citations: 1
  • Summary: From this understanding of the immune regulation of MS, the development of therapeutic strategies that target only pathogenic immune cells can be expected and the restoration of weakened immune regulatory functions may be a true disease-modifying treatment.
  • Evidence snippets:
  • Snippet 1 (score: 0.524) > Multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system, characterized by multiple lesions occurring temporally and spatially [1]. However, the details of the mechanism of onset have not been clarified. The diagnosis is usually confirmed by demonstrating temporal and spatial multifocal lesions through detailed medical history and neurological examination over time and ruling out other diseases [2]. On the other hand, patients presenting with symptoms primarily of optic nerve and spinal cord origin include those with neuromyelitis optica spectrum disorders (NMOSD), originally known as a non-recurring disease with an inflammatory background that severely damages the optic nerve and spinal cord in a relatively short period of time [3]. However, in recent years, it has become clear that recurrent pathology is common, and the involvement of serum anti-aquaporin 4 (AQP4) antibodies in pathogenesis is being elucidated [4]. Furthermore, among AQP4 antibody-positive patients, there are various patterns of NMOSD, such as those with lesions not only in the optic nerve and spinal cord but also in the brain; those with lesions only in the spinal cord or optic nerve; and those who are negative for AQP4 antibodies but have symptoms characteristic of NMOSD. > The currently used disease-modifying drugs can effectively reduce relapses but are not effective in primary progressive disease. Furthermore, it is impossible to halt the progression of the disorder once it enters the secondary progressive stage, even in the relapsing tolerant type. Therefore, it is considered important to diagnose and start treatment as early as possible. In this review, we summarize the genetic and environmental factors, pathological animal models, cellular and molecular mechanisms, and clinical treatment strategies of MS with our current understanding of the novel molecular mechanisms of pathogenesis (Table 1). The basic pathology of MS is "inflammatory demyelination" and many attempts have been made to find the cause of this inflammation [1,2].

[2] Optical Coherence Tomography and Magnetic Resonance Imaging in Multiple Sclerosis and Neuromyelitis Optica Spectrum Disorder

  • Authors: Praveena Manogaran, J. Hanson, Elisabeth D. Olbert, Christine Egger, C. Wicki et al.
  • Year: 2016
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/fa650dacd817d9a5f996bf7de0b40dc6afd0fcb8
  • DOI: 10.3390/ijms17111894
  • PMID: 27854301
  • PMCID: 5133893
  • Citations: 35
  • Influential citations: 1
  • Summary: This review focuses on the current knowledge of the role of the visual pathway using OCT and MRI in patients with MS and NMOSD, and emphasis is placed on studies that employ both MRI and OCT to investigate damage to the visual system in these diseases.
  • Evidence snippets:
  • Snippet 1 (score: 0.500) > Multiple sclerosis (MS) is a chronic autoimmune inflammatory disorder of the central nervous system (CNS) in which different environmental factors act on the basis of a multi-genetic trait [1,2]. It is characterized by focal demyelinating plaques and diffuse neurodegeneration throughout the white and gray matter [3,4]. Approximately two million people worldwide are affected by this disorder, and it is the most common non-traumatic neurological disability affecting young adults [5]. Neuromyelitis optica spectrum disorder (NMOSD) is a rare autoimmune astrocytopathic disease of the CNS that preferentially involves the optic nerve and spinal cord [6,7]. The identification of the disease-specific NMO-immunoglobulin G (NMO-IgG) and its effects on astrocytic aquaporin-4 (AQP4) water channels has helped to facilitate differentiation of NMOSD from MS [8]. Nevertheless, imaging and clinical manifestations frequently overlap, particularly in the early stages of the diseases and in NMOSD patients testing negative for AQP4-IgG antibodies [7]. The exact pathophysiological mechanisms behind MS and NMOSD have still not been fully elucidated; however, there is evidence that tissue injury and demyelination in MS is mediated by T-cell activity [9]. Axonal and neuronal atrophy is likely a secondary effect of inflammatory demyelination but can also occur as a result of independent subclinical disease activity [9]. Neuro-axonal degeneration (in addition to demyelination) has recently been considered more relevant in MS pathophysiology; it has been documented in both active and inactive lesions, distal to the areas affected by autoimmune inflammation, and early in the disease course [10]. Conversely, the pathophysiology in NMOSD predominantly involves the deposition of IgG and complement, resulting in a loss of AQP4 proteins on astrocytes and severe neuronal and axonal loss [6]. > Both diseases present with significant clinical and pathological heterogeneity between individuals.

[3] Research hotspots and emerging topics in neuromyelitis optica spectrum disorder treatment: Insights from a bibliometric analysis

  • Authors: Juan Wang, Guangbiao Cai, Shuang Xia, J. Qin, Ben Liu
  • Year: 2025
  • Venue: Medicine
  • URL: https://www.semanticscholar.org/paper/e16edbb1e19a145ebe90cb544ac347c2df815c38
  • DOI: 10.1097/MD.0000000000042850
  • PMID: 40489809
  • PMCID: 12150997
  • Summary: This bibliometric analysis provides for the first time a comprehensive framework and frontier hot spot analysis in the field of NMOSD treatment, offering references for researchers in the field and contributing to the further development of the field.
  • Evidence snippets:
  • Snippet 1 (score: 0.478) > Neuromyelitis optica spectrum disorder (NMOSD) encompasses a range of inflammatory conditions that are characterized by recurrent episodes, with the optic nerves and spinal cord being the main sites of involvement. From a microscopic perspective, patients produce a specific autoantibody known as aquaporin-4 immunoglobulin G antibodies (AQP4-IgG). This antibody binds to AQP4 on the astrocytic foot processes at the surface of microvessels, the spinal cord gray matter, the ocular globe, the subarachnoid space of the optic nerve, around the mesencephalic aqueduct, and the periventricular regions, forming immune complexes. This, in turn, activates the complement immune system to produce an immune response, leading to demyelination, neuronal damage, and necrosis. [1,2] Approximately 70% to 80% of individuals with NMOSD exhibit positive results for AQP4-IgG antibody testing. The antibody triggers the disease through various mechanisms, including inflammatory responses, amplification of immune responses, antibody-dependent cellular cytotoxicity, disruption of aquaporin function, early granulocyte recruitment, and complement-dependent cytotoxicity. Studies have shown that undiagnosed and untreated NMOSD patients are associated with disability and poor prognosis, and the degree of disability accumulates with each relapse. Therefore, preventing relapses is crucial in the disease management of NMOSD. [3] ith a deeper understanding of its pathological mechanisms, the therapy for NMOSD is rapidly evolving and gradually becoming a research focus. These treatment strategies aim to control the disease, reduce relapse rates, alleviate the progression of disability, and elevate the living standards of patients by precisely regulating the relevant molecular and cellular pathways. > Bibliometrics, functioning as a thorough and unbiased approach to scientific data analysis, offers an advantageous way to delve into the knowledge architecture, developmental trajectories, hotspots, trends, and the contributions of various researchers, institutions, and countries. [4]

[4] The Use of Human Mesenchymal Stem Cells as Therapeutic Agents for the in vivo Treatment of Immune-Related Diseases: A Systematic Review

  • Authors: Alessander Leyendecker Jr., C. Pinheiro, M. Amano, D. Bueno
  • Year: 2018
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/c68257f1169b10b00ea537555272b2ce76c263aa
  • DOI: 10.3389/fimmu.2018.02056
  • PMID: 30254638
  • PMCID: 6141714
  • Citations: 82
  • Influential citations: 2
  • Summary: The results obtained in this study open new avenues for the treatment of immune-related diseases through the administration of hMSCs and emphasize the importance of the conduction of further studies in this area.
  • Evidence snippets:
  • Snippet 1 (score: 0.477) > Finally, a study conducted by Ulusoy et al. (147) reported a decrease in the serum levels of anti-muscle-specific tyrosine kinase antibodies after the treatment with hMSCs. Likewise, this study described a reduction in the percentages of neuromuscular junction IgG in the serum and complement component three deposits in the muscles of mice treated with hMSCs. It can be, therefore, speculated that the reduction in the severity and clinical manifestations of the disease observed after hMSCs administration is a direct result of the inhibitory effect of these stem cells in activation and proliferation of B cells. As a consequence, the secretion of IgG autoantibodies such as the anti-acetylcholine receptor antibody and the anti-musclespecific tyrosine kinase antibody by hyperstimulated B-cells also decreases, culminating in the inhibition in the progression of the disease. > Neuromyelitis optica is an inflammatory, demyelinating, and autoimmune disease of the central nervous system, which selectively affects the spinal cord and optic nerves, simultaneously or sequentially. Symptoms of neuromyelitis optica include loss of vision, sensitivity changes, muscle weakness, spasticity, incoordination, ataxia, urinary and fecal incontinence, and autonomic dysfunctions in parts of the trunk and limbs supplied by nerves coming out of the spine below the spinal lesion (215). Clinical and serological evidence of autoimmunity associated with B cells has been observed in patients with neuromyelitis optica, in whom demyelinating lesions exhibit perivascular immunoglobulin deposition, local activation of the complement cascade and eosinophilic infiltration (216). Other mechanisms involved in this humoral response are the secretion of IL-2, anti-myelin autoantibodies, oligodendrocyte-associated anti-glycoprotein autoantibodies, and IgG autoantibodies against the astroglial water channel aquaporin-4 (217). In general, neuromyelitis optica attacks are more severe than those of multiple sclerosis and are commonly fatal (215).

[5] Neuromyelitis optica (NMO)‐IgG‐driven organelle reorganization in human iPSC‐derived astrocytes

  • Authors: Sukhee Cho, Hyein Lee, Minkyo Jung, Kirim Hong, Seung-Hwa Woo et al.
  • Year: 2021
  • Venue: The FASEB Journal
  • URL: https://www.semanticscholar.org/paper/d9653662b93a3c95c53f2aaee0b3dc5ef97ee834
  • DOI: 10.1096/fj.202100637R
  • PMID: 34460995
  • PMCID: 12316078
  • Citations: 6
  • Summary: It is observed that NMO‐IgG induces structural alterations in mitochondria and their association with the endoplasmic reticulum (ER) and lysosomes at the ultrastructural level, which potentially leads to impaired mitochondrial functions and dynamics, and human astrocytes display impaired mitochondrial bioenergetics and autophagy activity.
  • Evidence snippets:
  • Snippet 1 (score: 0.457) > Neuromyelitis optica (NMO) is a primary astrocytic disease associated with inflammation and secondary myelin loss in the central nervous system (CNS). 1 The presence of autoantibodies (NMO-IgG) in patient sera targeting aquaporin 4 (AQP4), a water channel, is an important clinical biomarker that plays a central role in disease pathogenesis. 2,3 In the CNS, AQP4 is predominantly expressed in astrocytes, especially on their end-foot processes. 4 Upon NMO-IgG binding to AQP4, endocytosis is initiated, which consequently reduces AQP4 membrane levels. 5,6 The interaction between NMO-IgG and astrocytic AQP4 leads to the synthesis of components of the complement system and cytokines, which contribute to pathogenesis in other cell types such as microglia. 7,8 While NMO-IgG plays a central role in disease pathogenesis, the cellular changes driven by NMO-IgG in astrocytes and their associated molecular mechanisms are largely unknown. > Astrocytes are key components of the CNS. They provide trophic support for synaptogenesis, maintain a homeostatic environment, regulate synaptic activity, and sustain the metabolic needs of neurons. [9][10][11] Dysfunctional astrocytes are associated with multiple CNS disorders, including epilepsy, inflammatory demyelinating diseases, metabolic disorders, and neurodegenerative disorders. 12 Changes in astrocyte morphology, gene expression, and intracellular organelle networks are largely linked to their functions. [13][14][15][16] Recent studies have suggested the importance of understanding the mechanisms of organelle remodeling and subsequent functional alterations in astrocytes under pathological conditions, such as neuroinflammation and neurodegeneration. [16][17][18][19] Fundamental biology of astrocytes and pathogenic changes in NMO has been uncovered by rodent systems, which provide the groundwork for human studies. [5][6][7][8][20][21][22][23] To complement animal models and further our understanding of pathogenic mechanisms in

[6] Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies

  • Authors: Edgar Carnero Contentti, J. Correale
  • Year: 2021
  • Venue: Journal of Neuroinflammation
  • URL: https://www.semanticscholar.org/paper/24d72ed7ca0debc3bd49c5d9a142536567cbf6d3
  • DOI: 10.1186/s12974-021-02249-1
  • PMID: 34530847
  • PMCID: 8444436
  • Citations: 259
  • Influential citations: 6
  • Summary: A descriptive review of the new evidence on NMOSD pathophysiology and of preliminary results from ongoing trials with new drugs is presented, highlighting promising treatment modalities as well as auspicious preclinical and clinical studies.
  • Evidence snippets:
  • Snippet 1 (score: 0.456) > During the last two decades, significant advances have been made in NMOSD, including: introduction of new diagnostic criteria (gray arrows), identification of biomarkers, better characterization of clinical phenotypes, improved prognosis and new therapeutic approaches (black arrows). AQP4 aquaporin-4, AQP4-ab aquaporin-4-antibodies, IgG immunoglobulin G, IPND International Panel for NMO Diagnosis, MOG myelin-oligodendrocyte glycoprotein, NMO neuromyelitis optica, NMOSD neuromyelitis optica spectrum disorder, TM transverse myelitis treatment of acute episodes, individual symptom management, and long-term relapse prevention. > Long-term relapse prevention includes treatments based on data from retrospective observations, and prospective observational studies without control groups. The most commonly used treatments include azathioprine (AZA), mycophenolate (MMF), and rituximab [18]. In the last 2 years however, four pivotal randomized clinical trials (RCT) have expanded the spectrum of drugs available for NMOSD patients. Phase 3 studies have shown significant relapse reduction compared to placebo, in patients treated with monoclonal antibodies against the interleukin-6 receptor ([IL-6R]; satralizumab) [19,20], against CD 19 present on CD19-expressing B cells (inebilizumab) [21], and against the C5 fraction of complement (eculizumab) [13]. This effect was particularly found in AQP4-ab-positive NMOSD patients in all three trials [13,19,20]. > We therefore present a review on the most relevant findings as well as the auspicious preclinical and clinical study results, in light of additional evidence on molecular mechanisms underlying NMOSD, and ongoing trials of new drugs for treating this condition.

[7] Neuromyelitis optica spectrum disorders: from pathophysiology to therapeutic strategies

  • Authors: Edgar Carnero Contentti, J. Correale
  • Year: 2021
  • Venue: Journal of Neuroinflammation
  • URL: https://www.semanticscholar.org/paper/c0667cc145e48c228cbffee6237be11a3785ab20
  • DOI: 10.1186/s12974-021-02249-1
  • Summary: A descriptive review of the new evidence on NMOSD pathophysiology and of preliminary results from ongoing trials with new drugs is presented, highlighting promising treatment modalities as well as auspicious preclinical and clinical studies.
  • Evidence snippets:
  • Snippet 1 (score: 0.456) > During the last two decades, significant advances have been made in NMOSD, including: introduction of new diagnostic criteria (gray arrows), identification of biomarkers, better characterization of clinical phenotypes, improved prognosis and new therapeutic approaches (black arrows). AQP4 aquaporin-4, AQP4-ab aquaporin-4-antibodies, IgG immunoglobulin G, IPND International Panel for NMO Diagnosis, MOG myelin-oligodendrocyte glycoprotein, NMO neuromyelitis optica, NMOSD neuromyelitis optica spectrum disorder, TM transverse myelitis treatment of acute episodes, individual symptom management, and long-term relapse prevention. > Long-term relapse prevention includes treatments based on data from retrospective observations, and prospective observational studies without control groups. The most commonly used treatments include azathioprine (AZA), mycophenolate (MMF), and rituximab [18]. In the last 2 years however, four pivotal randomized clinical trials (RCT) have expanded the spectrum of drugs available for NMOSD patients. Phase 3 studies have shown significant relapse reduction compared to placebo, in patients treated with monoclonal antibodies against the interleukin-6 receptor ([IL-6R]; satralizumab) [19,20], against CD 19 present on CD19-expressing B cells (inebilizumab) [21], and against the C5 fraction of complement (eculizumab) [13]. This effect was particularly found in AQP4-ab-positive NMOSD patients in all three trials [13,19,20]. > We therefore present a review on the most relevant findings as well as the auspicious preclinical and clinical study results, in light of additional evidence on molecular mechanisms underlying NMOSD, and ongoing trials of new drugs for treating this condition.

[8] Experimental mouse model of optic neuritis with inflammatory demyelination produced by passive transfer of neuromyelitis optica-immunoglobulin G

  • Authors: Nithi Asavapanumas, J. Ratelade, M. Papadopoulos, J. Bennett, M. Levin et al.
  • Year: 2014
  • Venue: Journal of Neuroinflammation
  • URL: https://www.semanticscholar.org/paper/199771378a4db5fed5222917704fba5ee63d7729
  • DOI: 10.1186/1742-2094-11-16
  • PMID: 24468108
  • PMCID: 3909205
  • Citations: 61
  • Influential citations: 5
  • Summary: Passive transfer of NMO-IgG and complement by continuous infusion near the optic chiasm in mice is sufficient to produce ON with characteristic NMO pathology, and should be useful in further studies of N MO pathogenesis mechanisms and therapeutics.
  • Evidence snippets:
  • Snippet 1 (score: 0.451) > Neuromyelitis optica (NMO) is an autoimmune inflammatory disease of the central nervous system that causes demyelinating lesions in optic nerve and spinal cord, leading to loss of visual and motor function [1][2][3]. A specific feature of NMO is the presence of serum immunoglobulin G (IgG) autoantibodies (NMO-IgG) against astrocyte water channel aquaporin-4 (AQP4) [4,5]. NMO pathogenesis is thought to involve NMO-IgG binding to AQP4 on astrocytes, which causes complement-and cell-mediated astrocyte cytotoxicity, inflammation, and blood-brain barrier (BBB) disruption, with secondary oligodendrocyte and neuron damage [6][7][8]. Current therapies of NMO include general immunosuppression, B-cell depletion and plasma exchange [9,10]. > Although optic neuritis (ON) with permanent loss of vision is a major clinical feature of NMO [11][12][13], adequate models of NMO ON are lacking. The particular sensitivity of the optic nerve in NMO suggests the need to study disease mechanisms and treatment responses in optic nerve-specific NMO models. Disease-relevant animal models of NMO are important for investigating pathogenesis mechanisms, such as the role of inflammatory effector cells [14][15][16] and for testing of potential therapeutics such as antibodies targeting AQP4 [17] or complement [18,19]. The original models of NMO involved administration of NMO-IgG to rats with pre-existing neuroinflammation produced by experimental autoimmune encephalomyelitis, in which immunization with a myelin oligopeptide produces an anti-myelin T-cell response [20][21][22]. Subsequently, a passive-transfer mouse model of NMO involving intracranial injection of NMO-IgG and human complement recapitulated key pathological findings in NMO, including loss of AQP4 and glial fibrillary acidic protein (GFA

[9] Progressive patterns of neurological disability in multiple sclerosis and neuromyelitis optica spectrum disorders

  • Authors: T. Akaishi, Toshiyuki Takahashi, T. Misu, Michiaki Abe, T. Ishii et al.
  • Year: 2020
  • Venue: Scientific Reports
  • URL: https://www.semanticscholar.org/paper/a5e9449cd7d204533f5484f7c4f77b96fef78acb
  • DOI: 10.1038/s41598-020-70919-w
  • PMID: 32807848
  • PMCID: 7431838
  • Citations: 65
  • Influential citations: 1
  • Summary: Clinical deterioration in NMOSD patients is irreversible and almost exclusively takes place at the timing of clinical attacks with stepwise accumulation of neurological disability, while changes in EDSS score can be seen apart from relapses in MS patients.
  • Evidence snippets:
  • Snippet 1 (score: 0.451) > The progressive patterns of neurological disability in multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) and the significance of clinical relapses to the progressions of neurological disability in these diseases have not been fully elucidated. In this study, to elucidate the impact of relapses to the progression of accumulated neurological disability and to identify the factors to affect the progression of neurological disability in MS and NMOSD, we followed 62 consecutive MS patients and 33 consecutive NMOSD patients for more than 5 years with the clinical symptoms, relapse occurrence, and Expanded Disability Status Scale (EDSS) in the chronic phase. All enrolled MS patients were confirmed to be negative for serum anti-myelin oligodendrocyte glycoprotein antibody. As a result, patients with NMOSD showed significantly severer neurological disability at 5 years from onset than MS patients. Progression in EDSS score was almost exclusively seen after clinical attacks in NMOSD, whereas progression could be observed apart from relapses in MS. Neurological disability did not change without attacks in NMOSD, whereas it sometimes spontaneously improved or deteriorated apart from relapses in MS (p < 0.001). In patients with MS, those with responsible lesions primarily in spinal cord were more likely to show such spontaneous improvement. In conclusion, clinical deterioration in NMOSD patients is irreversible and almost exclusively takes place at the timing of clinical attacks with stepwise accumulation of neurological disability. Meanwhile, changes in EDSS score can be seen apart from relapses in MS patients. Neurological disability in MS patients is partly reversible, and the patients with disease modifying drugs sometimes present spontaneous improvement of the neurological disability. > Multiple sclerosis (MS) and neuromyelitis optica spectrum disorders (NMOSD) are major autoimmune-related neurological diseases that predominantly impairs the central nervous system (CNS) but have distinct pathophysiological mechanisms 1,2 . Both diseases typically present recurrent clinical attacks with lesions in cerebrum, optic nerves, brainstem, and spinal cord 1,3 .

[10] Bioenergetic Failure in Rat Oligodendrocyte Progenitor Cells Treated with Cerebrospinal Fluid Derived from Multiple Sclerosis Patients

  • Authors: Deepali Mathur, A. Riffo-Campos, J. Castillo, J. Haines, Ó. G. Vidaurre et al.
  • Year: 2017
  • Venue: Frontiers in Cellular Neuroscience
  • URL: https://www.semanticscholar.org/paper/0c10bb85a037674a2360de1661c9858850536a46
  • DOI: 10.3389/fncel.2017.00209
  • PMID: 28775680
  • PMCID: 5517784
  • Citations: 11
  • Summary: The findings revealed downregulated expression of genes involved in carbohydrate metabolism, and that glucose metabolism impairment and reduced ATP availability for cellular damage repair clearly differentiate more benign forms from the most aggressive forms and worst prognosis in MS patients.
  • Evidence snippets:
  • Snippet 1 (score: 0.448) > In relapsing-remitting multiple sclerosis (RRMS) subtype, the patient's brain itself is capable of repairing the damage, remyelinating the axon and recovering the neurological function. Cerebrospinal fluid (CSF) is in close proximity with brain parenchyma and contains a host of proteins and other molecules, which influence the cellular physiology, that may balance damage and repair of neurons and glial cells. The purpose of this study was to determine the pathophysiological mechanisms underpinning myelin repair in distinct clinical forms of MS and neuromyelitis optica (NMO) patients by studying the effect of diseased CSF on glucose metabolism and ATP synthesis. A cellular model with primary cultures of oligodendrocyte progenitor cells (OPCs) from rat cerebrum was employed, and cells were treated with CSF from distinct clinical forms of MS, NMO patients and neurological controls. Prior to comprehending mechanisms underlying myelin repair, we determine the best stably expressed reference genes in our experimental condition to accurately normalize our target mRNA transcripts. The GeNorm and NormFinder algorithms showed that mitochondrial ribosomal protein (Mrpl19), hypoxanthine guanine phosphoribosyl transferase (Hprt), microglobulin β2 (B2m), and transferrin receptor (Tfrc) were identified as the best reference genes in OPCs treated with MS subjects and were used for normalizing gene transcripts. The main findings on microarray gene expression profiling analysis on CSF treated OPCs cells revealed a disturbed carbohydrate metabolism and ATP synthesis in MS and NMO derived CSF treated OPCs. In addition, using STRING program, we investigate whether gene-gene interaction affected the whole network in our experimental conditions.

[11] Differentiated pattern of complement system activation between MOG-IgG-associated disease and AQP4-IgG-positive neuromyelitis optica spectrum disorder

  • Authors: Eun Bin Cho, Ju-Hong Min, Patrick Waters, Miyoung Jeon, Eun-Seon Ju et al.
  • Year: 2024
  • Venue: Frontiers in Immunology
  • URL: https://www.semanticscholar.org/paper/5f3f33c0449de66063a546e4c16de7a5dac452e9
  • DOI: 10.3389/fimmu.2024.1320094
  • PMID: 38576611
  • PMCID: 10991751
  • Citations: 8
  • Summary: A higher prominence of complement pathway activation and subsequent C3 degradation in MOGAD compared to AQP4-NMOSD is indicated, implying a strong regulation of the complement system, implying its potential involvement in the pathogenesis of MOGAD through mechanisms that extend beyond TCC formation.
  • Evidence snippets:
  • Snippet 1 (score: 0.442) > Neuromyelitis optica spectrum disorders (NMOSD) are chronic inflammatory diseases of the central nervous system (CNS) that preferentially affects the optic nerve, spinal cord, and certain brain regions. The discovery of pathogenic antibodies that target aquaporin-4 (AQP4-immunoglobulin G [IgG]) facilitated the recognition of AQP4-IgG positive NMOSD (AQP4-NMOSD) as a distinct disease entity (1). Antibodies against myelin oligodendrocyte glycoprotein (MOG-IgG) were found more recently in a group of patients with demyelinating disease whose clinical features partially overlap with NMOSD and a new disease entity associated with MOG-IgG, called MOG antibody-associated disease (MOGAD), was suggested (2). The clinical phenotypes of MOGAD overlap with those of NMOSD but include a wider range of presenting phenotypes including acute disseminated encephalomyelitis (ADEM), optic neuritis, myelitis, or demyelinating brain lesions; however, its clinical course and prognosis differ from those of AQP4-NMOSD (2,3). > AQP4 is a major water channel protein in the CNS that is highly expressed in the astrocytic foot processes. Complement-dependent AQP4-IgG-mediated cytotoxicity is a major mechanism of astrocyte damage with secondary oligodendrocyte loss, and these lesions are associated with perivascular deposition of activated complements and inflammatory cell infiltration (4). On the other hand, it has not yet been determined how MOG-IgG contributes to MOGAD pathogenesis. MOG is a minor myelin protein predominantly localized at the outermost layer of the myelin sheaths and oligodendrocyte membranes (5).

[12] The Role of Gut Microbiota in Neuromyelitis Optica Spectrum Disorder

  • Authors: Shi-Qi Yao, Xiayin Yang, Ling-Ping Cen, Shaoying Tan
  • Year: 2024
  • Venue: International Journal of Molecular Sciences
  • URL: https://www.semanticscholar.org/paper/194c7b744b51683530862ea205d9e0f95486c489
  • DOI: 10.3390/ijms25063179
  • PMID: 38542152
  • PMCID: 10970017
  • Citations: 10
  • Summary: Research on the involvement of the gut microbiota in the pathophysiology of NMOSD and its possible pathogenic mechanisms is summarized, with Clostridium perfringens and Streptococcus confirmed to play a role by multiple studies.
  • Evidence snippets:
  • Snippet 1 (score: 0.440) > Neuromyelitis optica spectrum disorder (NMOSD) is a rare, disabling inflammatory disease of the central nervous system (CNS). Aquaporin-4 (AQP4)-specific T cells play a key role in the pathogenesis of NMOSD. In addition to immune factors, T cells recognizing the AQP4 epitope showed cross-reactivity with homologous peptide sequences in C. perfringens proteins, suggesting that the gut microbiota plays an integral role in the pathogenicity of NMOSD. In this review, we summarize research on the involvement of the gut microbiota in the pathophysiology of NMOSD and its possible pathogenic mechanisms. Among them, Clostridium perfringens and Streptococcus have been confirmed to play a role by multiple studies. Based on this evidence, metabolites produced by gut microbes, such as short-chain fatty acids (SCFAs), tryptophan (Trp), and bile acid (BA) metabolites, have also been found to affect immune cell metabolism. Therefore, the role of the gut microbiota in the pathophysiology of NMOSD is very important. Alterations in the composition of the gut microbiota can lead to pathological changes and alter the formation of microbiota-derived components and metabolites. It can serve as a biomarker for disease onset and progression and as a potential disease-modifying therapy.

[13] Long-Term Efficacy and Safety of Satralizumab in Patients With Neuromyelitis Optica Spectrum Disorder From the SAkuraMoon Open-Label Extension Study

  • Authors: Jeffrey L. Bennett, Kazuo Fujihara, Albert Saiz, A. Traboulsee, Benjamin M Greenberg et al.
  • Year: 2025
  • Venue: Neurology® Neuroimmunology & Neuroinflammation
  • URL: https://www.semanticscholar.org/paper/ddaca7d18b636f7c59a5b26aac620c1e0c5d18ff
  • DOI: 10.1212/NXI.0000000000200450
  • PMID: 40743487
  • PMCID: 12316463
  • Citations: 2
  • Summary: This study provides Class IV evidence that SAT is safe and effective in patients with NMOSD, supporting SAT as an effective maintenance therapy option for patients with AQP4-IgG+ NMOSD.
  • Evidence snippets:
  • Snippet 1 (score: 0.437) > Neuromyelitis optica spectrum disorder (NMOSD) is a rare, chronic, autoimmune disease, characterized by demyelinating lesions in the optic nerves, spinal cord, brainstem, and cerebrum. 1,2 The hallmark clinical manifestations of NMOSD are optic neuritis, resulting in vision loss, and longitudinally extensive transverse myelitis resulting in weakness, sensory impairment, and bladder and bowel dysfunction. 1,3 uaporin-4 immunoglobulin-G-seropositive (AQP4-IgG+) NMOSD generally follows a relapsing disease course, and patients are at persistent risk of relapse regardless of disease duration. 1 Disability and health-related quality-of-life worsening are driven by attacks/relapses, and chronic neurologic disability develops incrementally after attacks. 4 erefore, NMOSD management focuses on the treatment of acute attacks and aims to prevent future relapses, meaning that patients require lifelong preventative therapeutic options that are both safe and effective. 5,6 [9] IL-6, a pleiotropic cytokine implicated in the pathophysiology of AQP4-IgG+ NMOSD, plays a role in the immunopathogenic mechanisms upstream of AQP4-IgG-related effects, mediated through B cell-related and T cell-related pathways. 10,11 IL-6 induces T-cell polarization toward an inflammatory Th17 phenotype, inhibits T regulatory cell development, promotes B-cell differentiation into plasmablasts, and contributes to impaired integrity of the blood-brain barrier, thus enabling pathogenic antibodies and proinflammatory cells to enter the CNS. 10,11 [15][16] In the double-blind (DB) periods of the 2 pivotal phase 3 studies, treatment with SAT in combination with background immunosuppressive therapy (IST) (SAkuraSky) or as a monotherapy (SAkuraStar) significantly reduced relapse risk in adult and adolescent patients with AQP4-IgG+ NMOSD vs placebo (PBO). 13,14

[14] Comprehensive review of neuromyelitis optica and clinical characteristics of neuromyelitis optica patients in Puerto Rico

  • Authors: S. Zarei, James Eggert, Laura Franqui-Dominguez, Yonatan Carl, Fernando Boria et al.
  • Year: 2018
  • Venue: Surgical Neurology International
  • URL: https://www.semanticscholar.org/paper/a549c7aa8826272d20c1e908975f5d551622aacc
  • DOI: 10.4103/sni.sni_224_18
  • PMID: 30603227
  • PMCID: 6293609
  • Citations: 20
  • Influential citations: 2
  • Summary: This research will provide a comprehensive overview of all aspects of N MO, including epidemiology, environmental risk factors, genetic factors, molecular mechanism, symptoms, comorbidities and clinical differentiation, diagnosis, treatment, its management, and prognosis, and evaluate the demographic features and clinical phenotype of NMO patients in PR.
  • Evidence snippets:
  • Snippet 1 (score: 0.436) > Neuromyelitis optica (NMO) is an immune-mediated inflammatory disorder of the central nervous system. It is characterized by concurrent inflammation and demyelination of the optic nerve (optic neuritis [ON]) and the spinal cord (myelitis). Multiple studies show variations in prevalence, clinical, and demographic features of NMO among different populations. In addition, ethnicity and race are known as important factors on disease phenotype and clinical outcomes. There are little data on information about NMO patients in underserved groups, including Puerto Rico (PR). In this research, we will provide a comprehensive overview of all aspects of NMO, including epidemiology, environmental risk factors, genetic factors, molecular mechanism, symptoms, comorbidities and clinical differentiation, diagnosis, treatment, its management, and prognosis. We will also evaluate the demographic features and clinical phenotype of NMO patients in PR. This will provide a better understanding of NMO and establish a basis of knowledge that can be used to improve care. Furthermore, this type of population-based study can distinguish the clinical features variation among NMO patients and will provide insight into the potential mechanisms that cause these variations.

[15] Neuromyelitis Optica Spectrum Disorders: Clinical Perspectives, Molecular Mechanisms, and Treatments

  • Authors: Subramanian Thangaleela, B. Sivamaruthi, A. Radha, P. Kesika, C. Chaiyasut
  • Year: 2023
  • Venue: Applied Sciences
  • URL: https://www.semanticscholar.org/paper/c4ea13835c99020313ed6eda722e17420e6ab657
  • DOI: 10.3390/app13085029
  • Citations: 8
  • Summary: All possible recent studies related to molecular mechanisms, clinical perspectives, and treatment methodologies of the disease are provided, particularly focusing on recent developments in clinical criteria and therapeutic formulations.
  • Evidence snippets:
  • Snippet 1 (score: 0.436) > Neuromyelitis optica (NMO) is a rare autoimmune inflammatory disorder affecting the central nervous system (CNS), specifically the optic nerve and the spinal cord, with severe clinical manifestations, including optic neuritis (ON) and transverse myelitis. Initially, NMO was wrongly understood as a condition related to multiple sclerosis (MS), due to a few similar clinical and radiological features, until the discovery of the AQP4 antibody (NMO-IgG/AQP4-ab). Various etiological factors, such as genetic-environmental factors, medication, low levels of vitamins, and others, contribute to the initiation of NMO pathogenesis. The autoantibodies against AQP4 target the AQP4 channel at the blood–brain barrier (BBB) of the astrocyte end feet, which leads to high permeability or leakage of the BBB that causes more influx of AQP4-antibodies into the cerebrospinal fluid (CSF) of NMO patients. The binding of AQP4-IgG onto the AQP4 extracellular epitopes initiates astrocyte damage through complement-dependent cytotoxicity (CDC) and antibody-dependent cellular cytotoxicity (ADCC). Thus, a membrane attack complex is formed due to complement cascade activation; the membrane attack complex targets the AQP4 channels in the astrocytes, leading to astrocyte cell damage, demyelination of neurons and oligodendrocytes, and neuroinflammation. The treatment of NMOSD could improve relapse symptoms, restore neurological functions, and alleviate immunosuppression. Corticosteroids, apheresis therapies, immunosuppressive drugs, and B cell inactivating and complement cascade blocking agents have been used to treat NMOSD. This review intends to provide all possible recent studies related to molecular mechanisms, clinical perspectives, and treatment methodologies of the disease, particularly focusing on recent developments in clinical criteria and therapeutic formulations.

[16] Neuroprotective therapies for multiple sclerosis and other demyelinating diseases

  • Authors: P. Villoslada
  • Year: 2016
  • Venue: Multiple Sclerosis and Demyelinating Disorders
  • URL: https://www.semanticscholar.org/paper/18513effd17c9ab745065eafc95282d00453ffa8
  • DOI: 10.1186/s40893-016-0004-0
  • Citations: 33
  • Influential citations: 1
  • Summary: Improvement in the understanding of underlying biology, in the design of clinical trials specific for assessing neuroprotection, and new technologies for developing novel therapies for neuroprotection suggest a new avenue for treating MS, Optic Neuritis or Neuromyelitis Optica.
  • Evidence snippets:
  • Snippet 1 (score: 0.431) > Damage to the Central Nervous Systems (CNS) in Multiple Sclerosis (MS) seems to be mainly due to chronic inflammation of the CNS with superimposed bouts of inflammatory activity by the adaptive immune system. The immune mediated damage can be amplified by neurodegenerative mechanisms in damaged axons including anterograde or retrograde axonal or transynaptic degeneration, synaptic pruning and neuronal or oligodendrocyte death. As such, it is highly unlikely that CNS damage can be prevented using only immunomodulatory drugs. For this reason, neuroprotection, aimed at preventing axonal, neuronal, myelin, and oligodendrocyte damage and cell death in the presence of this toxic microenvironment is highly pursued in MS and other demyelinating diseases. Neuroprotective strategies target different processes including oxidative stress, ionic imbalance (sodium, potassium or calcium), energy depletion, trophic factor support, metabolites balance, excitotoxicity, apoptosis, remyelination, etc. Although none of these strategies have translated into approved drugs to date, improvement in the understanding of underlying biology, in the design of clinical trials specific for assessing neuroprotection, and new technologies for developing novel therapies for neuroprotection suggest a new avenue for treating MS, Optic Neuritis or Neuromyelitis Optica (NMO). Several of these therapies are now entering clinical phases and if successful, such strategies would improve patients’ quality of life, and will be even more critical for patients with progressive MS. In the event that such therapies target natural repair mechanisms rather than disease specific processes, they can potentially be useful for other brain diseases such as stroke, neurodegenerative diseases, brain trauma or epilepsy.

[17] Complement-dependent bystander injury to neurons in AQP4-IgG seropositive neuromyelitis optica

  • Authors: Tianjiao Duan, Alex J. Smith, A. Verkman
  • Year: 2018
  • Venue: Journal of Neuroinflammation
  • URL: https://www.semanticscholar.org/paper/ac8bc8f4ff0f66b966e404f0e008f7e8fbc138e7
  • DOI: 10.1186/s12974-018-1333-z
  • PMID: 30348195
  • PMCID: 6198534
  • Citations: 70
  • Influential citations: 1
  • Summary: The hypothesis that complement bystander injury, which involves diffusion to nearby cells of activated soluble complement components from complement-injured astrocytes, is a general phenomenon that may contribute to neuronal injury in NMO is tested and evidence that complement bystanderser injury may be ageneral phenomenon for brain cell injury following AQP4-IgG-targeted astroCyte death is provided.
  • Evidence snippets:
  • Snippet 1 (score: 0.430) > Aquaporin-4-immunoglobulin G (AQP4-IgG) seropositive neuromyelitis optica spectrum disorder (herein called NMO) is an autoimmune demyelinating disease of the central nervous system. NMO pathogenesis involves binding of AQP4-IgG autoantibodies to water channel AQP4 on astrocytes, resulting in complement-and cell-mediated astrocyte injury, inflammation, demyelination, and neuron loss [1][2][3]. Though demyelination and neuronal injury could be secondary consequences of astrocyte death and an inflammatory response, the rapid disease progression seen in some NMO patients [4,5] and the rapid pathological changes seen in animal models during in vivo imaging of lesion formation [6,7] suggest more direct mechanisms by which astrocyte injury produces neuronal injury and neurologic deficit. Several mechanisms have been proposed to account for neuronal injury in NMO, including excitotoxic damage following glutamate release from injured astrocytes [8,9] and secondary recruitment of granulocytes and cytotoxic T cells [10,11]. However, the role of excitotoxic mechanisms has been controversial [12,13], and although cellular mechanisms are probably important, they are unlikely to cause the immediate damage to surrounding cells following exposure to AQP4-IgG. > Complement activation is a major effector pathway in NMO. NMO pathology in humans shows centrovascular deposition of activated complement [14][15][16], and early clinical trials data support the efficacy of a complement inhibitor [17,18]. Complement-dependent NMO pathology is also seen in experimental animal models of NMO produced by passive transfer of AQP4-IgG [6,7,19]. We recently reported evidence for complement bystander injury to oligodendrocytes, in which complement activation following AQP4-IgG binding to AQP4 on astrocytes results in killing of nearby oligodendrocytes by a bystander mechanism involving local diffusion of activated, soluble complement components, leading to formation of the complement membrane attack complex (MAC

[18] Long-term Effects of IL-6 Receptor Blockade Therapy on Regulatory Lymphocytes and Neutrophils in Neuromyelitis Optica Spectrum Disorder

  • Authors: T. Matsuoka, Manabu Araki, Youwei Lin, Tomoko Okamoto, Ralf Gold et al.
  • Year: 2023
  • Venue: Neurology® Neuroimmunology & Neuroinflammation
  • URL: https://www.semanticscholar.org/paper/e1a506662cdf3585a5ab657ba30d687f27edf8d3
  • DOI: 10.1212/NXI.0000000000200173
  • PMID: 37863660
  • PMCID: 10691226
  • Citations: 14
  • Summary: In patients with active NMOSD not treated with molecular targeting drugs, reduction or deficiency in lymphocytes with regulatory potentials and activation of neutrophils is observed, however, introduction of anti–IL-6R therapy accompanied by tapering concomitant drugs corrected such abnormalities, which might contribute to persistent relapse prevention.
  • Evidence snippets:
  • Snippet 1 (score: 0.430) > Neuromyelitis optica spectrum disorder (NMOSD) is an autoimmune disease of the CNS, causing inflammatory damage to the optic nerve, spinal cord, brainstem, and the cerebral white matter. 1,2 Anti-aquaporin 4-antibody (AQP4-Ab) 1,3,4 is a surrogate marker for a core group of NMOSD with predominant astrocyte pathology. For such anti-AQP4-Ab-positive patients, disease-modifying drugs for multiple sclerosis (MS), such as interferon β, are not efficacious but rather harmful, [5][6][7] indicating the difference between NMOSD and MS in the immunopathogenesis. Until recently, corticosteroids and off-label immunosuppressive drugs or plasmapheresis were the only available treatment options for NMOSD. However, clinical trials based on the pathophysiology of NMOSD have provided several high-efficacy drugs, including the B-cell depleting drugs rituximab 8,9 and inebilizumab, 10 the anticomplement C5 drug eculizumab, 11 and the anti-IL-6R drug satralizumab. 12,13 Currently, the mechanism of action of each drug in vivo remains poorly understood, and no theoretical background is offered to select a drug for each patient. > This study was initiated before the approval of such drugs. 5][16][17] Recent phase 3 clinical trials revealed that the recycling anti-IL-6R monoclonal antibody satralizumab as add-on therapy 12 or as monotherapy 13 would significantly reduce relapses in anti-AQP4-Ab-positive NMOSD. However, because IL-6 is a pleiotropic cytokine involved in numerous biological responses, the mechanisms of IL-6R blockade therapy remain to be investigated further, particularly regarding the cellular immune profiling pretherapy and posttherapy, to clarify the important features of the therapy in comparison with other approved drugs.

[19] Abstracts

  • Authors: N. Turner, Schmid, L. Mahon
  • Year: 1917
  • Venue: ASN NEURO
  • URL: https://www.semanticscholar.org/paper/ac7be82f67b14aa621f838b8a8d56012eb36d038
  • DOI: 10.2337/diab.14.12.814
  • PMCID: 9720786
  • Summary: Results indicated that after intravenous sodium tolbutamide in duodenal ulcer subjects there was an increase in gastric secretion of acid, chloride, and potassium, as well as in volume of secretion, similar to, but milder than, those producible in reported studies utilizing insulin.
  • Evidence snippets:
  • Snippet 1 (score: 0.430) > The Astrocytes Role, Linking Basic Research, Clinical Characteristics, and Therapeutic Perspectives Violeta Millet 1,2,3 > Neuromyelitis Optica spectrum disorder (NMOSD), previously known as Devic Disease, is a chronic autoimmune inflammatory disease of the central nervous system characterized by secondary immune-mediated demyelination and consequent axonal damage. NMOSD clinically preferentially affects the optic nerves (optic neuritis) and the spinal cord (transverse myelitis). An important advance in understanding neuromyelitis Optica (NMO) pathogenesis was the discovery of the AQP-4 antibody that targets the water channel membrane protein aquaporin-4 (AQP-4). AQP-4 is expressed on the end-feet membranes of astrocytes along the blood-brain barrier of astrocytes, in ependymal cell membranes, and in Muller cells present on the fovea in the retina. Serum Aqp4 antibodies existed in approximately 80-90% of patients with NMO and more than half of patients with NMOSD. The binding of AQP-4-IgG to AQP-4 causes complementdependent cytotoxicity, antibody-dependent cellular cytotoxicity, and the consequent astrocyte injury. Animal models allow us to understand the pathogenic mechanisms in the immune cascade and help the development of potential drug therapies. Diverse in vivo, ex vivo, and in vitro experimental systems have been used but an ideal animal model of NMO with spontaneous AQP-4-IGG positive optic neuritis and transverse myelitis has yet to be created. Large research is in progress on the pathogenesis, genetic background, serum biomarkers, and optic coherence tomography segmentation. Novel drugs targeting the complement cascade system, IL-6R, and B cells are being studied. Recently, novel therapeutic strategies focused on the induction of antigen-specific immune tolerance by administrating tolerogenic immune-modifying nanoparticles are being developed. Deep research in immune tolerance-based therapies in NMO is likely to be a major step toward improving the treatment outcomes of the disease. In many retina degenerative diseases, the progressive

[20] Optic neuritis in demyelinating diseases: study of 38 cases

  • Authors: J. Ferreira, Cristiane Rebello Gomes de Souza Fontes, Carolina do Val Ferreira Ramos, O. Nascimento
  • Year: 2023
  • Venue: Arquivos de Neuro-Psiquiatria
  • URL: https://www.semanticscholar.org/paper/5e9a36468c07948b8f617b71839ac9992ece204c
  • DOI: 10.1055/s-0044-1792093
  • PMID: 39675357
  • PMCID: 11646668
  • Citations: 1
  • Summary: Patients with optic neuritis as the initial symptom were predominantly female, aged between 21 and 40 years, and of predominantly white ethnicity, with a higher prevalence of MS and a direct relationship between the healthcare sector and the time to diagnosis became evident.
  • Evidence snippets:
  • Snippet 1 (score: 0.429) > A growing area of study with notable development recently has been neuroimmunology, both in terms of diagnostic methods and treatments. The main clinical disorders involved in this area of neurology are multiple sclerosis (MS), neuromyelitis optica spectrum disorder (NMOSD), and myelin oligodendrocyte glycoprotein-immunoglobulin G (MOG-IgG)-associated disorders (MOGADs). ][3][4] Characterized by their autoimmune etiology, demyelinating diseases (DDs) exhibit in their pathophysiology an attack to the myelin sheath, the substance that covers the axons in the central nervous system. This condition, exemplified by multiple sclerosis (MS), transverse myelitis, leukodystrophies and optic neuritis (ON), presents a wide range of clinical manifestations and temporal profiles of development, including the possibility of relapses. 5 ptic neuritis, an inflammation of the optic nerve, can be caused by various factors, including genetic aspects (a strong association with the HLA-DRB1 and HLA-B27 genes), external influences (trauma and/or toxins), and the activation of a cross-immune response to infections, which is the main mechanism. 6,7 egarding the activation mechanism of the cross-immune response, it can occur with the reaction of serological markers of the type immunoglobulin G (IgG), including MOG-IgG, which targets the MOG glycoprotein in the myelin present in oligodendrocytes. Another influential immunoglobulin in the process is NMO-IgG, which reacts against the aquaporin-4 present in astrocytic cells. 5,7 epending on the stimulus response to the neuronal structuring cells and the impairment of propagation of the nerve impulse from the retina to the lateral geniculate bodies, the possibility of visual impairments arises, presenting with the most typical symptoms of ON: ocular pain on movement with acute loss of unilateral visual acuity.

Notes

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  • No synthesis or second-stage model call is performed.