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

E Angot, P Brundin - Parkinsonism & related disorders, 2009 - Elsevier
E Angot, P Brundin
Parkinsonism & related disorders, 2009Elsevier
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 …
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.
Elsevier