# MicroRNA as Potential Biomarkers and Their Pathogenesis in Multiple System Atrophy

**Authors:** Ming-Che Kuo, Shao-Ying Cheng, Meng-Ling Chen, Ruey-Meei Wu

PMC · DOI: 10.3390/ijms27041878 · International Journal of Molecular Sciences · 2026-02-15

## TL;DR

This review explores how microRNAs may contribute to the development of multiple system atrophy and could serve as potential biomarkers or treatment targets.

## Contribution

The paper provides a synthesis of current evidence on miRNA involvement in MSA pathogenesis and their potential as biomarkers.

## Key findings

- Dysregulated miRNA profiles are linked to α-synuclein aggregation and neuroinflammation in MSA.
- miRNAs may influence oligodendrocyte dysfunction and demyelination in the disease process.
- miRNAs could serve as potential biomarkers and therapeutic targets for MSA.

## Abstract

Multiple system atrophy (MSA) is a rare, rapidly progressive neurodegenerative disorder characterized by autonomic dysfunction, Parkinsonism, and cerebellar ataxia. While the pathological hallmark of MSA is the accumulation of α-synuclein in oligodendrocytes and formation of glial cytoplasmic inclusions (GCIs), the precise etiopathogenesis, accurate biomarkers, and promising therapeutic targets remain elusive. This review synthesizes current evidence regarding the role of microRNAs (miRNAs) in MSA, focusing on how small non-coding RNAs mediate gene–environment interactions contributing to disease pathogenesis. We explore dysregulated miRNA profiles in MSA, their impact on α-synuclein aggregation, neuroinflammation, demyelinating process, and oligodendrocyte dysfunction, and their potential as biomarkers and therapeutic targets. Understanding the complex interplay between miRNAs, genetic susceptibility, and environmental factors may provide critical insights into MSA pathophysiology and open new avenues for therapeutic intervention.

## Linked entities

- **Diseases:** Multiple system atrophy (MONDO:0007803), cerebellar ataxia (MONDO:0000437)

## Full-text entities

- **Genes:** TPPP (tubulin polymerization promoting protein) [NCBI Gene 11076] {aka TPPP/p25, TPPP1, p24, p25, p25alpha}, EFEMP2 (EGF-like fibulin extracellular matrix protein 2) [NCBI Gene 30008] {aka ARCL1B, FBLN4, MBP1, UPH1}, NFKB1 (nuclear factor kappa B subunit 1) [NCBI Gene 4790] {aka CVID12, EBP-1, KBF1, NF-kB, NF-kB1, NF-kappa-B1}, MIR331 (microRNA 331) [NCBI Gene 442903] {aka MIRN331, hsa-mir-331, mir-331}, LRRK2 (leucine rich repeat kinase 2) [NCBI Gene 120892] {aka AURA17, DARDARIN, PARK8, RIPK7, ROCO2}, AKT1 (AKT serine/threonine kinase 1) [NCBI Gene 207] {aka AKT, PKB, PKB-ALPHA, PRKBA, RAC, RAC-ALPHA}, MIR219A2 (microRNA 219a-2) [NCBI Gene 407003] {aka MIR219-2, MIRN219-2, hsa-mir-219a-2, mir-219a-2}, PIK3CB (phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit beta) [NCBI Gene 5291] {aka P110BETA, PI3K, PI3KBETA, PIK3C1}, IL1A (interleukin 1 alpha) [NCBI Gene 3552] {aka IL-1 alpha, IL-1A, IL1, IL1-ALPHA, IL1F1}, MIR206 (microRNA 206) [NCBI Gene 406989] {aka MIRN206, miRNA206, mir-206}, MIR133B (microRNA 133b) [NCBI Gene 442890] {aka MIRN133B, miRNA133B, mir-133b}, MIR19B1 (microRNA 19b-1) [NCBI Gene 406980] {aka C13orf25, MIR19B, MIRH1, MIRHG1, MIRN19B1, miR-19b-1}, MIR223 (microRNA 223) [NCBI Gene 407008] {aka MIRN223, miRNA223, mir-223}, MIR346 (microRNA 346) [NCBI Gene 442911] {aka MIRN346, hsa-mir-346, miR-346, miRNA346}, MIR205 (microRNA 205) [NCBI Gene 406988] {aka MIRN205, mir-205}, MIR935 (microRNA 935) [NCBI Gene 100126325] {aka MIRN935, hsa-mir-935, mir-935}, MIR155 (microRNA 155) [NCBI Gene 406947] {aka MIRN155, miRNA155, mir-155}, MIR184 (microRNA 184) [NCBI Gene 406960] {aka EDICT, MIRN184, miR-184}, MIR181C (microRNA 181c) [NCBI Gene 406957] {aka MIRN181C, mir-181c}, POU2F1 (POU class 2 homeobox 1) [NCBI Gene 5451] {aka OCT1, OTF1, Oct1Z, oct-1B}, MIR20A (microRNA 20a) [NCBI Gene 406982] {aka C13orf25, MIR20, MIRH1, MIRHG1, MIRN20, MIRN20A}, MIR148B (microRNA 148b) [NCBI Gene 442892] {aka MIRN148B, mir-148b}, SNCA (synuclein alpha) [NCBI Gene 6622] {aka NACP, PARK1, PARK4, PD1}, MIR543 (microRNA 543) [NCBI Gene 100126335] {aka MIRN543, hsa-mir-543, mir-543}, MIR202 (microRNA 202) [NCBI Gene 574448] {aka MIRN202, hsa-mir-202, mir-202}, DGCR8 (DGCR8 microprocessor complex subunit) [NCBI Gene 54487] {aka C22orf12, DGCRK6, Gy1, pasha}, MIR369 (microRNA 369) [NCBI Gene 442914] {aka MIR369-3, MIRN369, MIRN369-3, hsa-mir-369, mir-369}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, MIR7-3 (microRNA 7-3) [NCBI Gene 407045] {aka MIRN7-3, hsa-mir-7-3, mir-7-3}, SLC1A1 (solute carrier family 1 member 1) [NCBI Gene 6505] {aka DCBXA, EAAC1, EAAT3, SCZD18, hEAAC1}, MIRLET7B (microRNA let-7b) [NCBI Gene 406884] {aka LET7B, MIRNLET7B, hsa-let-7b, let-7b}, MIR30A (microRNA 30a) [NCBI Gene 407029] {aka MIRN30A, mir-30a}, MBP (myelin basic protein) [NCBI Gene 4155], her15.2 (hairy and enhancer of split-related 15, tandem duplicate 2) [NCBI Gene 359836] {aka her15, her15b, hes5, hes5-like}, VPS35 (VPS35 retromer complex component) [NCBI Gene 55737] {aka MEM3, PARK17}, TPO (thyroid peroxidase) [NCBI Gene 7173] {aka MSA, TDH2A, TPX}, MIR1295A (microRNA 1295a) [NCBI Gene 100302178] {aka MIR1295, MIRN1295, hsa-mir-1295, hsa-mir-1295a, mir-1295a}, PRKN (parkin RBR E3 ubiquitin protein ligase) [NCBI Gene 5071] {aka AR-JP, LPRS2, PARK2, PDJ}, MIR19A (microRNA 19a) [NCBI Gene 406979] {aka C13orf25, MIRH1, MIRHG1, MIRN19A, hsa-mir-19a, miR-19a}, CEBPA (CCAAT enhancer binding protein alpha) [NCBI Gene 1050] {aka C/EBP-alpha, CEBP}, MIR25 (microRNA 25) [NCBI Gene 407014] {aka MIRN25, hsa-mir-25, miR-25}, MIR1293 (microRNA 1293) [NCBI Gene 100302220] {aka MIRN1293, hsa-mir-1293, mir-1293}, NOTCH3 (notch receptor 3) [NCBI Gene 4854] {aka CADASIL, CADASIL1, CARASIL1, CASIL, FPLD1, IMF2}, MIR451A (microRNA 451a) [NCBI Gene 574411] {aka MIR451, MIRN451, hsa-mir-451, hsa-mir-451a, mir-451a}, sox6 (SRY-box transcription factor 6) [NCBI Gene 567154] {aka fc35a10, fc50e03, sox-lz, sox6b, wu:fc35a10, wu:fc50e03}, MIR410 (microRNA 410) [NCBI Gene 574434] {aka MIRN410, hsa-mir-410, mir-410}, dre-mir-138 (microRNA 138) [NCBI Gene 100033661] {aka dre-mir-138-1, mir138}, MIR34A (microRNA 34a) [NCBI Gene 407040] {aka MIRN34A, miRNA34A, mir-34, mir-34a}, LILRB1 (leukocyte immunoglobulin like receptor B1) [NCBI Gene 10859] {aka CD85J, ILT-2, ILT2, LIR-1, LIR1, MIR-7}, MIR30D (microRNA 30d) [NCBI Gene 407033] {aka MIRN30D, mir-30d}, TP53 (tumor protein p53) [NCBI Gene 7157] {aka BCC7, BMFS5, LFS1, P53, TRP53}, MIR484 (microRNA 484) [NCBI Gene 619553] {aka MIRN484, hsa-mir-484, mir-484}, TGFB1 (transforming growth factor beta 1) [NCBI Gene 7040] {aka CAEND1, CED, DPD1, IBDIMDE, LAP, TGF-beta1}, PARK7 (Parkinsonism associated deglycase) [NCBI Gene 11315] {aka DJ-1, DJ1, GATD2, HEL-S-67p}, MIR183 (microRNA 183) [NCBI Gene 406959] {aka MIRN183, miR-183, miRNA183}, MSMB (microseminoprotein beta) [NCBI Gene 4477] {aka HPC13, IGBF, MSP, MSPB, PN44, PRPS}, MIR17 (microRNA 17) [NCBI Gene 406952] {aka MIR17-5p, MIR91, MIRN17, MIRN91, hsa-mir-17, miR-17}, MIR23A (microRNA 23a) [NCBI Gene 407010] {aka MIRN23A, hsa-mir-23a, miRNA23A, mir-23a}, PTEN (phosphatase and tensin homolog) [NCBI Gene 5728] {aka 10q23del, BZS, CWS1, DEC, GLM2, MHAM}, MIR34C (microRNA 34c) [NCBI Gene 407042] {aka MIRN34C, miRNA34C, mir-34c}
- **Diseases:** OL (MESH:D056784), cerebellar ataxia (MESH:D002524), Parkinsonian syndrome (MESH:D020734), inflammation (MESH:D007249), injury to (MESH:D014947), neurodegeneration (MESH:D019636), ALS (MESH:D000690), astrogliosis (MESH:D005911), MSA-C (MESH:D019578), demyelinating process (MESH:D003711), mitochondrial dysfunction (MESH:D028361), CBD (OMIM:303800), Parkinsonism (MESH:D010302), ataxic (MESH:D001039), PD (MESH:D010300), corticobasal degeneration (MESH:D000088282), AD (MESH:D000544), cancer (MESH:D009369), progressive supranuclear palsy (MESH:D013494), autophagic (MESH:C536522), Movement Disorder (MESH:D009069), alpha-synculeinopathy (MESH:D000795), Neuroinflammation (MESH:D000090862), autonomic dysfunction (MESH:D001342), alpha-synucleinopathies (MESH:D000080874), DLB (MESH:D020961), CNS disorder (MESH:D002493)
- **Chemicals:** paraffin (MESH:D010232), taurine (MESH:D013654), TPPP (-), lipid (MESH:D008055), glutamate (MESH:D018698), PFF (MESH:C412892), formalin (MESH:D005557), fatty acid (MESH:D005227)
- **Species:** Caenorhabditis elegans (species) [taxon 6239], Mus musculus (house mouse, species) [taxon 10090], Homo sapiens (human, species) [taxon 9606]
- **Cell lines:** GC-4 — Mus musculus (Mouse), Conditionally immortalized cell line (CVCL_6633), HEK293 — Homo sapiens (Human), Transformed cell line (CVCL_0045)

## Full text

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## References

93 references — full list in the complete paper: https://tomesphere.com/paper/PMC12941356/full.md

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Source: https://tomesphere.com/paper/PMC12941356