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Review
, 15 Suppl 3, S143-7

Dissecting the Potential Molecular Mechanisms Underlying Alpha-Synuclein Cell-To-Cell Transfer in Parkinson's Disease

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Review

Dissecting the Potential Molecular Mechanisms Underlying Alpha-Synuclein Cell-To-Cell Transfer in Parkinson's Disease

Elodie Angot et al. Parkinsonism Relat Disord.

Abstract

Alpha-synuclein (alpha-syn) aggregation is central to neuropathological changes in Parkinson's disease. The aggregates spread within the central nervous system according to a very predictable pattern. A prion-like transmission of alpha-syn aggregates has been recently proposed to explain this propagation pattern. First, we review the growing evidence for such a mechanism. This process is likely to occur in three consecutive steps: (i) exit of alpha-syn template from the donor cell, (ii) entry to the recipient cell and (iii) initiation of the nucleation. In a second part, we discuss the possible underlying mechanisms for each of these steps, based on our current knowledge about how cells handle alpha-syn but also other proteins involved in neurodegenerative diseases with a prion-like propagation. Finally, we discuss which molecular species of alpha-syn (monomer, oligomer, fibril) could be the seeding-competent species and whether this seeding process could be a common mechanism in neurodegenerative diseases.

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