Multiple system atrophy: at the crossroads of cellular, molecular and genetic mechanisms.

Nat Rev Neurosci

Division of Neurobiology, Department of Neurology, Medical University Innsbruck, Innsbruck, Austria.

Published: June 2023

Multiple system atrophy (MSA) is a rare oligodendroglial α-synucleinopathy characterized by neurodegeneration in striatonigral and olivopontocerebellar regions and autonomic brain centres. It causes complex cumulative motor and non-motor disability with fast progression and effective therapy is currently lacking. The difficulties in the diagnosis and treatment of MSA are largely related to the incomplete understanding of the pathogenesis of the disease. The MSA pathogenic landscape is complex, and converging findings from genetic and neuropathological studies as well as studies in experimental models of MSA have indicated the involvement of genetic and epigenetic changes; α-synuclein misfolding, aggregation and spreading; and α-synuclein strain specificity. These studies also indicate the involvement of myelin and iron dyshomeostasis, neuroinflammation, mitochondrial dysfunction and other cell-specific aspects that are relevant to the fast progression of MSA. In this Review, we discuss these findings and emphasize the implications of the complexity of the multifactorial pathogenic cascade for future translational research and its impact on biomarker discovery and treatment target definitions.

Download full-text PDF

Source
http://dx.doi.org/10.1038/s41583-023-00697-7DOI Listing

Publication Analysis

Top Keywords

multiple system
8
system atrophy
8
fast progression
8
msa
5
atrophy crossroads
4
crossroads cellular
4
cellular molecular
4
molecular genetic
4
genetic mechanisms
4
mechanisms multiple
4

Similar Publications

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!