Differential Membrane Binding and Seeding of Distinct α-Synuclein Fibrillar Polymorphs.

ABSTRACT: The aggregation of the protein α-synuclein (α-Syn) leads to different synucleinopathies. We recently showed that structurally distinct fibrillar α-Syn polymorphs trigger either Parkinson's disease or multiple system atrophy hallmarks in vivo. Here, we establish a structural-molecular basis for these observations. We show that distinct fibrillar α-Syn polymorphs bind to and cluster differentially at the plasma membrane in both primary neuronal cultures and organotypic hippocampal slice cultures from wild-type mice. We demonstrate a polymorph-dependent and concentration-dependent seeding. We show a polymorph-dependent differential synaptic redistribution of α3-Na⁺/K⁺-ATPase, GluA2 subunit containing α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors, and Glu

SUBMITTER: Shrivastava AN 

PROVIDER: S-EPMC7091477 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature