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Mucopolysaccharidosis

Disease Pathophysiology Research Report

2026-02-10
Falcon MONDO:0019249 Model: Edison Scientific Literature 13 citations

Disease Pathophysiology Research Report

Target Disease - Disease Name: Mucopolysaccharidosis (MPS) - MONDO ID: MONDO_0019249 (mucopolysaccharidosis) (derived from OpenTargets search metadata) - Category: Mendelian

1) Core Pathophysiology: Concepts, Definitions, and Current Understanding - Definition and unifying mechanism: MPS comprise inherited lysosomal storage disorders caused by deficiency of specific lysosomal hydrolases or sulfatases required for ordered degradation of glycosaminoglycans (GAGs). Primary substrates accumulate in lysosomes as proteoglycan-derived HS, DS, CS, KS, and HA, causing multi-organ dysfunction including CNS, skeletal, and cardiac disease (ago2024molecularmechanismsin pages 2-3, ago2024molecularmechanismsin pages 1-2). “MPSs are a group of inborn errors of the metabolism caused by a deficiency in the lysosomal enzymes required to break down…glycosaminoglycans (GAGs). These GAGs accumulate over time…disrupt…autophagy, and mitochondrial function…increase oxidative stress and activate innate immunity and inflammation” (IJMS, Jan 2024; https://doi.org/10.3390/ijms25021113) (ago2024molecularmechanismsin pages 1-2). - Staged progression: Recent synthesis highlights a sequence from reversible early storage to irreversible organ injury: “(1) disruption of substrate degradation with pathogenic changes in lysosomal function, (2) cellular dysfunction, secondary/tertiary accumulation (GM2/GM3 ganglioside, etc.), and inflammatory process, and (3) progressive tissue/organ damage and cell death (e.g., skeletal dysplasia, CNS impairment)” (IJMS, Jan 2024) (ago2024molecularmechanismsin pages 1-2). The same review emphasizes limits of current ERT/HSCT and rationale for BBB-penetrant strategies (ago2024molecularmechanismsin pages 2-3). - Systems perspective of lysosomal dysfunction: Beyond storage, lysosomes regulate vesicle trafficking, signaling, and autophagy; their dysfunction propagates organelle stress, oxidative injury, and inflammation. MPS “perturbs intracellular trafficking and autophagy,” and GAGs can activate innate immunity with cytokine induction; mitochondrial dysfunction contributes to inflammation and ROS elevation (K. Mikołajczak 2025; overview) (mikołajczak2025lysosomalstoragediseases pages 1-4, mikołajczak2025lysosomalstoragediseases pages 10-13).

2) Molecular Pathways and Cellular Processes Affected - Primary substrate accumulation by GAG species and subtypes: Representative mapping—MPS I (IDUA deficiency; HS/DS), MPS II (IDS deficiency; HS/DS), MPS IIIA/IIIB (SGSH/NAGLU; HS), MPS IVA (GALNS; KS±CS), MPS VI (ARSB; DS) (ago2024molecularmechanismsin pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, ago2024molecularmechanismsin pages 2-3). - Secondary storage: Accumulation of gangliosides (GM2, GM3) is reported as secondary/tertiary storage during progression (IJMS, 2024) (ago2024molecularmechanismsin pages 1-2). - Autophagy-lysosome pathway alterations: In MPS IIIB models, “metabolic rewiring and autophagy inhibition correct lysosomal storage disease,” with AMPK inhibition reducing HS storage and NK1 (HGF spliced variant) engaging PI3K/Akt, decreasing autophagy/lysosome markers (BCN1, LC3, LAMP1) (iScience, Mar 2024; https://doi.org/10.1016/j.isci.2024.108959) (scarcella2024metabolicrewiringand pages 10-12). These experiments provide mechanistic links among energy sensing (AMPK), PI3K/Akt signaling, and autophagy flux in the context of lysosomal HS storage (scarcella2024metabolicrewiringand pages 10-12). - Mitochondrial dysfunction and metabolic shifts: Brain metabolomics in MPS IIIB indicate broad rewiring (e.g., altered lactate and glutamine), consistent with mitochondrial/energy pathway disruption (iScience, 2024) (scarcella2024metabolicrewiringand pages 10-12). Reviews emphasize mitochondrial dysfunction accompanying GAG accumulation (IJMS, 2024) (ago2024molecularmechanismsin pages 1-2) and oxidative stress in MPS (overview) (mikołajczak2025lysosomalstoragediseases pages 1-4). - ER and Golgi stress; trafficking defects: Transcriptomics in neuronopathic MPS fibroblasts showed dysregulation of organelle-associated genes and EM evidence of structural disruptions—particularly Golgi apparatus fragmentation and ER stress markers. Up-regulated PDIA3 and MFGE8, down-regulated ARL6IP6, ABHD5, PDE4DIP, YIPF5, CLDN11; increased GM130 (GOLGA2) expression; mechanistic links to impaired ER-to-Golgi transport and Golgi fragmentation (CIMB, Mar 2024; https://doi.org/10.3390/cimb46030169) (wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10). The study notes that Golgi fragmentation “can precede neuronal cell death,” and perturbations in GRASP55/65 alter HS/CS synthesis and secretion, directly linking Golgi structure to GAG handling (wisniewska2024cellularorganellerelatedtranscriptomic pages 16-18). - Neuroinflammation and innate immune signaling: Reviews and cross-LSD analyses implicate microglial/astrocyte activation with upregulated cytokines/chemokines, and highlight TLR pathways and inflammasome activation in LSDs, also relevant to MPS; authors synthesize “pro-inflammatory immunological mediators” in LSD neuroinflammation (Biomedicines, Apr 2023; https://doi.org/10.3390/biomedicines11041067) (wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10). Contemporary MPS-focused reviews underscore a “profound relationship between immunity and MPS,” with complex inflammatory pathways (IJMS, 2024) (ago2024molecularmechanismsin pages 2-3). - Synaptic and circuit dysfunction: Neuronopathic MPS subtypes (e.g., MPS III) show pronounced CNS involvement with organelle stress signatures that plausibly impact synaptic homeostasis; organelle gene changes (e.g., GOLGA2, PDIA3) and mitochondrial stress are consistent with synaptic/autophagic deficits that drive neurodegeneration, though direct synaptic electrophysiology data were not retrieved in this evidence batch (CIMB, 2024; IJMS, 2024) (wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10, ago2024molecularmechanismsin pages 1-2). - Skeletal dysplasia mechanisms: Threshold storage in bone (notably growth plate) engages chondrocytes/osteoblasts/osteoclasts and becomes refractory to reversal once exceeded (IJMS, 2024) (ago2024molecularmechanismsin pages 2-3). Connective-tissue GAG storage (e.g., KS in MPS IVA; DS in MPS VI) disrupts ECM organization, secretion/trafficking, and growth plate architecture (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3, wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10). - Cardiac valve/myocardial disease: Reviews capture multi-system involvement with heart valves and myocardium impacted by GAG deposition and secondary inflammatory/oxidative mechanisms (IJMS, 2024; overview 2025) (ago2024molecularmechanismsin pages 2-3, mikołajczak2025lysosomalstoragediseases pages 10-13).

3) Key Molecular Players - Genes/Proteins (HGNC): IDUA (MPS I), IDS (MPS II), SGSH (MPS IIIA), NAGLU (MPS IIIB), GALNS (MPS IVA), ARSB (MPS VI). Additional organelle/stress markers: GOLGA2 (GM130), PDIA3, MFGE8, ARL6IP6, ABHD5, PDE4DIP, YIPF5, CLDN11; lysosome/autophagy markers LAMP1, LC3, BECN1; signaling axes AMPK, PI3K/Akt (ago2024molecularmechanismsin pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10, scarcella2024metabolicrewiringand pages 10-12). - Chemical entities (metabolites/small molecules; CHEBI): Heparan sulfate (HS), dermatan sulfate (DS), chondroitin sulfate (CS), keratan sulfate (KS), hyaluronan (HA); gangliosides GM2/GM3 (secondary storage); pathway modulators used experimentally (AICAr, SBI-0206965) and NK1 protein therapy concept (iScience 2024) (ago2024molecularmechanismsin pages 1-2, scarcella2024metabolicrewiringand pages 10-12). - Cell types (CL): Neurons, microglia (CL:0000129), astrocytes (CL:0000127), chondrocytes, osteoblasts, osteoclasts, fibroblasts (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2). - Anatomical locations (UBERON): Brain (UBERON:0000955), spinal cord, heart/valves (UBERON:0001911), growth plate cartilage (UBERON:0002418), bone, connective tissues (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3).

4) Biological Processes (GO terms) Disrupted - Lysosomal organization/function and autophagy: GO:0005773 (vacuole/lysosome), GO:0006914 (autophagy), GO:0016236 (macroautophagy), GO:0006629 (lipid metabolism) (ago2024molecularmechanismsin pages 1-2, scarcella2024metabolicrewiringand pages 10-12). - Innate immune/inflammatory signaling: GO:0006954 (inflammatory response), GO:0002224 (TLR signaling) and inflammasome-related pathways (supported at review level for LSDs with MPS relevance) (wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10, ago2024molecularmechanismsin pages 2-3). - Organelle stress and trafficking: GO:0006457 (protein folding), GO:0006888 (ER to Golgi vesicle-mediated transport), GO:0007030 (Golgi organization), GO:0007005 (mitochondrion organization) (wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 16-18, wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10). - ECM organization and skeletal development: GO:0030198 (extracellular matrix organization), GO:0001501 (skeletal system development) (ago2024molecularmechanismsin pages 2-3, ago2024molecularmechanismsin pages 1-2).

5) Cellular Components - Key loci of pathology: Lysosomes (GO:0005764/0005773), autophagosomes (GO:0005776), ER (GO:0005783), Golgi (GO:0005794), mitochondria (GO:0005739), synapses (GO:0045202) (ago2024molecularmechanismsin pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 16-18, scarcella2024metabolicrewiringand pages 10-12).

6) Disease Progression: Sequence of Events - Early/reversible storage: Initial HS/DS/KS/CS/HA accumulation within lysosomes (often as proteoglycans) with cellular stress responses that may be reversible if treated early (IJMS, 2024) (ago2024molecularmechanismsin pages 1-2). - Escalation: Lysosomal dysfunction leads to autophagy impairment, ER/Golgi stress, impaired trafficking and secretion, mitochondrial dysfunction with oxidative stress, and activation of innate immunity (microglia/astrocytes). Secondary/tertiary storage of gangliosides (GM2/GM3) emerges (IJMS, 2024; overview 2025) (ago2024molecularmechanismsin pages 1-2, mikołajczak2025lysosomalstoragediseases pages 1-4). - Organ damage: Progressive neuronal synaptic/circuit dysfunction and neurodegeneration; growth plate and bone dysplasia becoming refractory beyond storage thresholds; heart valve/myocardial pathology; multi-organ failure (IJMS, 2024) (ago2024molecularmechanismsin pages 2-3, ago2024molecularmechanismsin pages 1-2).

7) Phenotypic Manifestations and Mechanistic Links (HPO terms suggested) - Neurocognitive regression, behavioral disturbances, seizures (HPO:0001263, HPO:0000708): Associated with HS-driven neuroinflammation, autophagy/mitochondrial dysfunction, and organelle stress in neuronopathic MPS (IJMS 2024; CIMB 2024) (ago2024molecularmechanismsin pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2). - Skeletal dysplasia (HPO:0002652), short stature (HPO:0004322), joint contractures (HPO:0001371): Linked to GAG storage in cartilage/bone, secretory and ECM disorganization, chondrocyte dysfunction, and inflammation (IJMS 2024) (ago2024molecularmechanismsin pages 2-3, ago2024molecularmechanismsin pages 1-2). - Cardiac valvular disease (HPO:0001657), cardiomyopathy (HPO:0001638): Driven by storage/inflammation/oxidative stress in valves and myocardium (IJMS 2024; overview) (ago2024molecularmechanismsin pages 2-3, mikołajczak2025lysosomalstoragediseases pages 10-13).

8) Current Applications and Real-World Implementations (mechanistic perspective) - Enzyme replacement therapy (ERT) and HSCT: Cross-correction concept underlies current care. However, IV ERT has limited CNS efficacy due to BBB; HSCT carries donor/GvHD risks and is timing-sensitive. New strategies (intrathecal/intracerebroventricular ERT; receptor-mediated “molecular Trojan horse” enzymes) are proposed to target CNS and bone (IJMS, Jan 2024; https://doi.org/10.3390/ijms25021113) (ago2024molecularmechanismsin pages 2-3). “Several potential treatments…that can penetrate the blood–brain barrier and bone have been proposed…including targeting peptides and molecular Trojan horses…Gene therapy trials with AAV, ex vivo LV…are proposed and/or underway” (IJMS, 2024) (ago2024molecularmechanismsin pages 1-2). - Experimental pathway modulation: In MPS IIIB cells/brain, AMPK inhibition and PI3K/Akt activation (via NK1) reduce HS storage and normalize autophagy-lysosome markers, supporting metabolism–autophagy–lysosome crosstalk as a therapeutic lever (iScience, Mar 2024) (scarcella2024metabolicrewiringand pages 10-12).

9) Relevant Statistics and Data (recent) - Incidence: Approximate overall MPS incidence cited as ~1 in 20,000 live births (review synthesis) (ago2024molecularmechanismsin pages 1-2). - Quantitative molecular readouts in MPS IIIB models: AMPK inhibition reduced HS storage and lysosomal vacuolization after 24 h; brain metabolomics revealed significant changes in lactate and glutamine, among others (p/q values significant; detailed figures in iScience 2024) (scarcella2024metabolicrewiringand pages 10-12).

10) Embedded Artifact: Subtype-to-mechanism summary table | Subtype | Causal gene (HGNC) | Enzyme name | Primary stored GAG(s) | Key affected cells (CL terms) | Key organs/tissues (UBERON terms) | Key disrupted processes (GO terms) | Selected molecular notes | Evidence (citation IDs) | |---|---|---|---|---|---|---|---|---| | MPS I | IDUA | alpha-L-iduronidase | Heparan sulfate (HS); Dermatan sulfate (DS) | Microglia (CL:0000129), Astrocytes (CL:0000127), Chondrocytes | Brain (UBERON:0000955); Heart (UBERON:0001911); Growth plate cartilage (UBERON:0002418) | Lysosomal vacuole (GO:0005773); Autophagy (GO:0006914); Inflammatory response (GO:0006954) | Primary HS/DS accumulation → lysosomal dysfunction, secondary substrate perturbation, neuroinflammation and skeletal damage | (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, mikołajczak2025lysosomalstoragediseases pages 1-4) | | MPS II | IDS | iduronate 2-sulfatase | Heparan sulfate (HS); Dermatan sulfate (DS) | Microglia (CL:0000129), Astrocytes (CL:0000127), Osteoblasts/Chondrocytes | Brain (UBERON:0000955); Heart (UBERON:0001911); Growth plate cartilage (UBERON:0002418) | Lysosomal dysfunction (GO:0005773); Autophagy (GO:0006914); Inflammatory response (GO:0006954) | CNS involvement varies with residual IDS activity; systemic GAG deposition drives skeletal and cardiac pathology | (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3, mikołajczak2025lysosomalstoragediseases pages 1-4) | | MPS IIIA | SGSH | N-sulfoglucosamine sulfohydrolase | Heparan sulfate (HS) (predominantly neuronal storage) | Microglia (CL:0000129), Astrocytes (CL:0000127), Neurons | Brain (UBERON:0000955); Spinal cord | Lysosome/vacuole (GO:0005773); Autophagy (GO:0006914); Inflammatory response (GO:0006954) | Neuronopathic phenotype: HS-driven microglial activation, organelle (ER/Golgi) stress and altered organelle gene expression linked to neurodegeneration | (ago2024molecularmechanismsin pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10) | | MPS IIIB | NAGLU | alpha-N-acetylglucosaminidase | Heparan sulfate (HS) | Microglia (CL:0000129), Astrocytes (CL:0000127), Neurons | Brain (UBERON:0000955); Peripheral tissues | Lysosome (GO:0005773); Autophagy (GO:0006914); Inflammatory response (GO:0006954) | Autophagy–lysosome dysregulation and metabolic rewiring (AMPK/PI3K-Akt changes) correct storage in models; metabolic/mitochondrial perturbation accompanies HS storage | (scarcella2024metabolicrewiringand pages 10-12, ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2) | | MPS IVA | GALNS | galactosamine (N-acetyl)-6-sulfatase | Keratan sulfate (KS) ± chondroitin sulfate (CS) | Chondrocytes, Osteoblasts, Fibroblasts; (microglia/astrocytes in rare CNS cases) | Growth plate cartilage (UBERON:0002418); Bone; Heart (UBERON:0001911) | Lysosomal dysfunction (GO:0005773); ECM organization; Autophagy (GO:0006914) | Predominant skeletal/connective-tissue disease (KS accumulation); Golgi/ER trafficking and secretion disturbances affect GAG handling and matrix assembly | (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3, wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10) | | MPS VI | ARSB | arylsulfatase B | Dermatan sulfate (DS) | Chondrocytes, Osteoclasts/Osteoblasts, Fibroblasts | Growth plate cartilage (UBERON:0002418); Heart (valves) (UBERON:0001911); Skin | Lysosomal dysfunction (GO:0005773); Autophagy (GO:0006914); Inflammatory response (GO:0006954) | Severe somatic/skeletal disease from DS storage; inflammation and oxidative stress contribute to progressive tissue damage | (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3, mikołajczak2025lysosomalstoragediseases pages 1-4) |

Table: Compact mapping of key MPS subtypes showing causal genes, enzymes, principal stored GAGs, affected cells/tissues, disrupted GO processes, brief molecular notes, and source citations; useful as an ontology-ready summary for disease knowledgebases. Evidence is drawn from the provided context (mikołajczak2025lysosomalstoragediseases pages 1-4, mikołajczak2025lysosomalstoragediseases pages 10-13).

Gene/Protein Annotations and Ontology Mapping - HGNC: IDUA, IDS, SGSH, NAGLU, GALNS, ARSB; organelle/stress markers: GOLGA2, PDIA3, MFGE8, ARL6IP6, ABHD5, PDE4DIP, YIPF5, CLDN11 (ago2024molecularmechanismsin pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10, scarcella2024metabolicrewiringand pages 10-12). - GO Biological Processes: autophagy (GO:0006914), inflammatory response (GO:0006954), ER to Golgi transport (GO:0006888), Golgi organization (GO:0007030), mitochondrial organization (GO:0007005), ECM organization (GO:0030198) (scarcella2024metabolicrewiringand pages 10-12, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 16-18, ago2024molecularmechanismsin pages 2-3). - Cellular Components: lysosome/vacuole (GO:0005773), ER (GO:0005783), Golgi (GO:0005794), mitochondrion (GO:0005739), synapse (GO:0045202) (ago2024molecularmechanismsin pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 16-18). - Cell Types (CL): microglia (CL:0000129), astrocyte (CL:0000127), neuron, chondrocyte, osteoblast, osteoclast, fibroblast (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3, wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2). - Anatomical (UBERON): brain (UBERON:0000955), heart (UBERON:0001911), growth plate cartilage (UBERON:0002418), bone (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3). - Chemical Entities (CHEBI): heparan sulfate, dermatan sulfate, chondroitin sulfate, keratan sulfate, hyaluronan; GM2/GM3 gangliosides; AICAr; SBI-0206965 (ago2024molecularmechanismsin pages 1-2, scarcella2024metabolicrewiringand pages 10-12).

Expert Opinions and Analysis - Contemporary reviews converge on an expanded view of lysosomal biology, where primary GAG storage triggers multi-organelle stress responses and maladaptive signaling, notably in autophagy-lysosome and innate immune axes. The staged progression model rationalizes why early intervention is crucial for CNS and skeletal outcomes and why bone disease is especially refractory after a threshold of growth-plate storage is exceeded (ago2024molecularmechanismsin pages 2-3, ago2024molecularmechanismsin pages 1-2). Emerging experimental data (MPS IIIB) corroborate that tuning energy sensors (AMPK) and autophagy-related signaling (PI3K/Akt) can reduce storage and normalize lysosomal/autophagic markers, suggesting tractable nodes for adjunctive therapy alongside substrate- or gene-directed approaches (scarcella2024metabolicrewiringand pages 10-12). Organelle transcriptomics and ultrastructural data tie neuronopathic phenotypes to ER/Golgi/mitochondrial derangements that likely impinge on synaptic function and neuronal viability (wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 16-18).

Citations with URLs and Dates - Ago Y, Rintz E, Musini KS, Ma Z, Tomatsu S. Molecular Mechanisms in Pathophysiology of Mucopolysaccharidosis and Prospects for Innovative Therapy. International Journal of Molecular Sciences. 2024 Jan;25(2):1113. URL: https://doi.org/10.3390/ijms25021113 (ago2024molecularmechanismsin pages 1-2, ago2024molecularmechanismsin pages 2-3). - Scarcella M, et al. Metabolic rewiring and autophagy inhibition correct lysosomal storage disease in mucopolysaccharidosis IIIB. iScience. 2024 Mar;27(3):108959. URL: https://doi.org/10.1016/j.isci.2024.108959 (scarcella2024metabolicrewiringand pages 10-12). - Wiśniewska K, et al. Cellular Organelle-Related Transcriptomic Profile Abnormalities in Neuronopathic Types of MPS. Current Issues in Molecular Biology. 2024 Mar;46:2678–2700. URL: https://doi.org/10.3390/cimb46030169 (wisniewska2024cellularorganellerelatedtranscriptomic pages 1-2, wisniewska2024cellularorganellerelatedtranscriptomic pages 16-18, wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10). - Pandey MK. Exploring Pro-Inflammatory Immunological Mediators: Neuroinflammation in LSDs. Biomedicines. 2023 Apr;11(4):1067. URL: https://doi.org/10.3390/biomedicines11041067 (wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10). - Mikołajczak K. Lysosomal storage diseases as a complex pathophysiological and clinical problem—part one. 2025 (overview). Mechanistic statements on inflammation/oxidative stress and multi-organ involvement used as supportive background (mikołajczak2025lysosomalstoragediseases pages 1-4, mikołajczak2025lysosomalstoragediseases pages 10-13).

Limitations - Some mechanistic details (e.g., definitive roles for TLR4, inflammasome, cGAS-STING specifically in MPS brain) are supported here at the review level across LSDs and MPS-focused reviews without new 2024 primary data in this evidence batch. Direct synaptic physiology evidence and detailed cardiac histopathology from 2023–2024 primary studies were not captured in the retrieved set; claims were framed accordingly (wisniewska2024cellularorganellerelatedtranscriptomic pages 7-10, ago2024molecularmechanismsin pages 2-3).

References

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