Bio-Bits - LAG3, a Novel Receptor for Misfolded alpha-Synuclein


A recent study has identified the lymphocyte-activation gene 3 (LAG3), also known as CD223, as the binding receptor for misfolded α-synuclein (Mao et al., Neurodegeneration 2016). LAG3 is a transmembrane protein belonging to the immunoglobulin superfamily with diverse biologic effects on T cell function. LAG3 is enriched in the spleen and thymus, and is also expressed in neurons throughout the central nervous system (CNS), including dopaminergic neurons (DAs) which are highly susceptible to degeneration in Parkinson’s disease (PD). LAG3 was found to associate with and lead to internalization of pathologic, pre-formed fibrils (PFFs) of α-synuclein. This interaction was proposed as a mechanism for the cell-to-cell transmission of toxic α-synuclein species in neurons, which has been viewed as a potential driver of PD pathogenesis. These findings highlight a novel CNS function for LAG3, a protein traditionally known to play a role in the immune system.

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