Biomedical Research Foundation Academy Of AthensAcademy Of Athens
Research Highlights :Autophagy mediates the clearance of oligodendroglial SNCA/alpha-synuclein and TPPP/p25A in multiple system atrophy models


Maria Xilouri, Panagiota Mavroeidi and colleagues recently published a paper in Autophagy


Multiple system atrophy (MSA) is a rare neurological disorder associated with the degeneration of nerve cells in specific areas of the brain. The disease shares common clinical features with Parkinson’s disease and is characterized by the accumulation of cytoplasmic inclusions (glial cytoplasmic inclusions, GCIs) filled with the neuronal protein alpha-synuclein within oligodendrocytes. Oligodendrocytes are a selective type of glial cells that provide support and insulation to neuronal axons, creating the myelin sheath around them. We have previously shown that accumulation of oligodendroglial alpha-synuclein and the oligodendroglia-specific phoshoprotein TPPP/p25Α predisposes oligodendrocytes to form such inclusions, which eventually lead to neuronal demise (

In the current study we have extensively characterized the manner of clearance of these pathological proteins, using both cell lines and primary murine oligodendroglial cultures. Collectively, our study reveals that the endogenous oligodendroglial alpha-synuclein and TPPP/p25Α, the two main GCI- components involved in MSA pathogenesis, are degraded via the autophagy lysosome pathway and that conversely, the presence of pathological alpha-synuclein can impair the activity of the lysosome. Importantly, our data compellingly suggest that augmentation of the selective autophagic pathways chaperone-mediated autophagy and macroautophagy prevents the accumulation/aggregation of alpha-synuclein and/or TPPP/p25A in oligodendrocytes.

Further validation in pre-clinical models of the disease may pave the way for the use of autophagy modulators or gene-based approaches as therapeutic approaches to halt or attenuate disease progression in human MSA.



Autophagy mediates the clearance of oligodendroglial SNCA/alpha-synuclein and TPPP/p25A in multiple system atrophy models.
Mavroeidi P, Arvanitaki F, Vetsi M, Becker S, Vlachakis D, Jensen PH, Stefanis L, Xilouri M.
Autophagy. 2022 Jan 9:1-30. doi: 10.1080/15548627.2021.2016256. Online ahead of print.
PMID: 35000546