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@article{laferriere_similar_2022,
	title = {Similar neuronal imprint and no cross-seeded fibrils in α-synuclein aggregates from {MSA} and Parkinson’s disease},
	volume = {8},
	issn = {2373-8057},
	url = {https://www.nature.com/articles/s41531-021-00264-w},
	doi = {10.1038/s41531-021-00264-w},
	abstract = {Abstract
            Aggregated alpha-synuclein (α-syn) is a principal constituent of Lewy bodies ({LBs}) and glial cytoplasmic inclusions ({GCIs}) observed respectively inside neurons in Parkinson’s disease ({PD}) and oligodendrocytes in multiple system atrophy ({MSA}). Yet, the cellular origin, the pathophysiological role, and the mechanism of formation of these inclusions bodies ({IBs}) remain to be elucidated. It has recently been proposed that α-syn {IBs} eventually cause the demise of the host cell by virtue of the cumulative sequestration of partner proteins and organelles. In particular, the hypothesis of a local cross-seeding of other fibrillization-prone proteins like tau or {TDP}-43 has also been put forward. We submitted sarkosyl-insoluble extracts of post-mortem brain tissue from {PD}, {MSA} and control subjects to a comparative proteomic analysis to address these points. Our studies indicate that: (i) α-syn is by far the most enriched protein in {PD} and {MSA} extracts compared to controls; (ii) {PD} and {MSA} extracts share a striking overlap of their sarkosyl-insoluble proteomes, consisting of a vast majority of mitochondrial and neuronal synaptic proteins, and (iii) other fibrillization-prone protein candidates possibly cross-seeded by α-syn are neither found in {PD} nor {MSA} extracts. Thus, our results (i) support the idea that pre-assembled building blocks originating in neurons serve to the formation of {GCIs} in {MSA}, (ii) show no sign of amyloid cross-seeding in either synucleinopathy, and (iii) point to the sequestration of mitochondria and of neuronal synaptic components in both {LBs} and {GCIs}.},
	pages = {10},
	number = {1},
	journaltitle = {npj Parkinson's Disease},
	shortjournal = {npj Parkinsons Dis.},
	author = {Laferrière, Florent and Claverol, Stéphane and Bezard, Erwan and De Giorgi, Francesca and Ichas, François},
	urldate = {2022-02-09},
	date = {2022-12},
	langid = {english},
	keywords = {peer-reviewed},
}