Cell-to-cell transmission of toxic forms of α-Synuclein (αS) is thought to underlie disease progression in Parkinson’s disease. Here we describe our efforts to understand the role of neurexin 1β, a presynaptic cell adhesion glycoprotein, in cellular internalization of both monomer and aggregated αS. Our prior work found that extracellular N-linked glycoproteins, and neurexin 1β, specifically, had a key role in neuronal uptake of αS. Using a variety of biophysical methods, we characterize the interactions of wild-type and Parkinson’s disease associated point variants of αS with neurexin 1β. Our work provides insight into molecular details of the interaction between αS and neurexin 1β and the resulting cellular internalization of αS.

Identifying molecular details of neurexin 1β-driven cellular uptake of α-Syncuclein

ACS Spring Meeting 2021

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