Molecular Neurobiology

, Volume 56, Issue 10, pp 7003–7021 | Cite as

Alterations in Striatal microRNA-mRNA Networks Contribute to Neuroinflammation in Multiple System Atrophy

  • Taeyeon Kim
  • Elvira Valera
  • Paula DesplatsEmail author


Multiple systems atrophy (MSA) is a rare neurodegenerative disorder characterized by the accumulation of α-synuclein in glial cells and neurodegeneration in the striatum, substantia nigra, and cerebellum. Aberrant miRNA regulation has been associated with neurodegeneration, including alterations of specific miRNAs in brain tissue, serum, and cerebrospinal fluid from MSA patients. Still, a causal link between deregulation of miRNA networks and pathological changes in the transcriptome remains elusive. We profiled ~ 800 miRNAs in the striatum of MSA patients in comparison to healthy individuals to identify specific miRNAs altered in MSA. In addition, we performed a parallel screening of 700 transcripts associated with neurodegeneration to determine the impact of miRNA deregulation on the transcriptome. We identified 60 miRNAs with abnormal levels in MSA brains that are involved in extracellular matrix receptor interactions, prion disease, inflammation, ubiquitin-mediated proteolysis, and addiction pathways. Using the correlation between miRNA expression and the abundance of their known targets, miR-124-3p, miR-19a-3p, miR-27b-3p, and miR-29c-3p were identified as key regulators altered in MSA, mainly contributing to neuroinflammation. Finally, our study also uncovered a potential link between Alzheimer’s disease (AD) and MSA pathologies that involves miRNAs and deregulation of BACE1. Our results provide a comprehensive appraisal of miRNA alterations in MSA and their effect on the striatal transcriptome, supporting that aberrant miRNA expression is highly correlated with changes in gene transcription associated with MSA neuropathology, in particular those driving inflammation, disrupting myelination, and potentially impacting α-synuclein accumulation via deregulation of autophagy and prion mechanisms.


Multiple systems atrophy microRNA Alpha-synuclein Neurodegeneration Inflammation Transcription 



multiple system atrophy




glial cytoplasmic inclusions


long intervening non-coding RNA




cerebrospinal fluid


Alzheimer’s disease


Parkinson’s disease


control cases


extracellular matrix


dementia with Lewy bodies


gene set enrichment analysis


differentially expressed genes


ingenuity pathway analysis


amyloid precursor protein



We are grateful to the University of California, San Diego Shiley-Marcos AD Research Center, and the Johns Hopkins Medical Institution Brain Resource Center for the provision of brain tissue. The authors want to thank Dr. Elsa Molina, Director of the Sanford Stem Cell Clinical Center, and UCSD-Sanford Consortium for Regenerative Medicine for technical assistance with array processing.

Funding information

This work was supported by the NIH grant NS092803 from NINDS to P.D. The UCSD Shiley-Marcos Alzheimer’s Disease Research Center is supported by the NIH grant AG05131.

Supplementary material

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Authors and Affiliations

  1. 1.Department of NeuroscienceUniversity of California San DiegoLa JollaUSA
  2. 2.Department of PathologyUniversity of California San DiegoLa JollaUSA

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