Genetic evidence for a functional association between Parkinson's disease proteins leucine-rich repeat kinase 2 and α-synuclein during axonal transport.

ABSTRACT: Mutations in α-synuclein (α-syn) and LRRK2 cause familial Parkinson's disease (fPD), yet how these proteins functionally interact remain ambiguous. We previously showed that α-syn undergoes bi-directional transport within axons and influences mitochondrial health, while other studies suggested that LRRK2-G2019S disrupts the axonal transport of autophagic vesicles and mitochondria. Here we tested the hypothesis that α-syn and LRRK2 are functionally linked during axonal transport. Expression of human LRRK2-WT in Drosophila larval nerves caused modest CSP-containing axonal blockages whereas no defects were seen in LRRK2 loss of function mutants in contrast to other proteins directly involved in axonal transport. Surprisingly, fPD mutations in the GTPase (LRRK2-Y1699C) and

SUBMITTER: Chakraborty P 

PROVIDER: S-EPMC12833220 | biostudies-literature | 2025

REPOSITORIES: biostudies-literature