Dissecting the potential molecular mechanisms underlying α-synuclein cell-to-cell transfer in Parkinson's disease

• Published in: Parkinsonism & related disorders Vol. 15; pp. S143 - S147
• Main Authors: Angot, Elodie, Brundin, Patrik
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01.12.2009
• Subjects: alpha-Synuclein - metabolism; Animals; Cell Communication - physiology; Clinical Medicine; Humans; Klinisk medicin; Medical and Health Sciences; Medicin och hälsovetenskap; Neurologi; Neurology; Neurons - metabolism; Neurons - pathology; Parkinson Disease - metabolism; Parkinson Disease - pathology; Parkinson's disease; Prion-like propagation; Protein Transport - physiology; α-Synuclein; α-Synuclein; Parkinson's disease; Prion-like propagation
• ISSN: 1353-8020; 1873-5126; 1873-5126
• DOI: 10.1016/S1353-8020(09)70802-8

Summary α-Synuclein (α-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 α-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 α-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 α-syn but also other proteins involved in neurodegenerative diseases with a prion-like propagation. Finally, we discuss which molecular species of α-syn (monomer, oligomer, fibril) could be the seeding-competent species and whether this seeding process could be a common mechanism in neurodegenerative diseases.