Data from: Aplp1 interacts with Lag3 to facilitates transmission of pathologic α-synuclein

Pathologic α-synuclein (α-syn) spreads from cell-to-cell, in part, through
binding to the lymphocyte-activation gene 3 (Lag3). Here we report that
amyloid β precursor-like protein 1 (Aplp1) interacts with Lag3 that
facilitates the binding, internalization, transmission, and toxicity of
pathologic α-syn. Deletion of both Aplp1 and Lag3 eliminates the loss of
dopaminergic neurons and the accompanying behavioral deficits induced by
α-syn preformed fibrils (PFF). Anti-Lag3 prevents the internalization of
α-syn PFF by disrupting the interaction of Aplp1 and Lag3, and blocks the
neurodegeneration induced by α-syn PFF in vivo. The identification of
Aplp1 and the interplay with Lag3 for α-syn PFF induced pathology advances
our understanding of the molecular mechanism of cell-to-cell transmission
of pathologic α-syn and provides additional targets for therapeutic
strategies aimed at preventing neurodegeneration in Parkinson’s disease
and related α-synucleinopathies.