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Benjamin Dehay et al. dans Movement Disorders

Propagation de l’ α-synucléine: Où en sommes nous ? / α-Synuclein Propagation: Where Are We At?

Le 6 octobre 2015

Dehay B, Vila M, Bezard E, Brundin P, Kordower JH. Alpha-synuclein propagation: New insights from animal models. Mov Disord. 2015 Sep 8. doi: 10.1002/mds.26370

Abstract PubMed: Aggregation of alpha-synuclein is implicated in several neurodegenerative diseases collectively termed synucleinopathies. Emerging evidence strongly implicates cell-to-cell transmission of misfolded alpha-synuclein as a common pathogenetic mechanism in synucleinopathies. ....more

 "In 2008, observations of Lewy pathology in post-mortem studies of dopamine neurons grafted to the brains of Parkinson’s disease (PD) patients kindled the idea that PD is a prion-like disorder.
The alpha-synuclein (α-syn) aggregates found in the transplanted neurons displayed several features that are characteristic of Lewy pathology, e.g. they were ubiquitinated, Thioflavin S-positive and stained for the P129S post-translational modification. A review of all post-mortem studies of transplanted PD patients suggests that α-syn aggregates develop in transplants following a lag time of one decade after surgery. The observations made in transplanted neurons might also explain why Lewy pathology develops progressively, following a stereotypic pattern consistent with neural connections (so called Braak stages), in the non-grafted PD brain.

While Braak and coworkers proposed that a "neurotropic virus" explains why α-syn aggregates seem to first develop in anterior olfactory structures and the dorsal motor nucleus of the vagal nerve in PD, reaching the substantia nigra dopaminergic neurons only several years later, the emerging evidence now suggests that misfolded α-syn itself is the “spreading agent”. Thus, misfolded α-syn behaves in a prion-like fashion. This gradual propagation of α-syn pathology throughout the nervous system might also in part explain the progression of symptoms in PD." 

  (click on image) "Since 2008, numerous experiments in cell cultures first, followed by the use of different experimental paradigms in animal models have clearly demonstrated that α-syn transfers between cells. This review provides an update of this booming research field and on how research in animal models supports the concept that misfolded α-syn spreads from cell to cell and describes how findings in animal models might relate to the disease process in humans. Finally, we discuss the current underlying molecular and cellular mechanisms and future therapeutic strategies targeting α-syn propagation".

Benjamin Dehay / Inserm / Team : Pathophysiology of parkinson's syndrome / IMN
Dernière mise à jour le 07.10.2015