Vexed mediates non-cell autonomous loss of dopaminergic neurons
Authors: Jacinta Davis; Elizabeth Kolaski; Daniel Babcock
Affiliation: Lehigh University
Keywords: a. neural degeneration; c. innate immunity
Parkinson’s Disease (PD) is the most prevalent movement disorder with about 10 million people worldwide affected. The hallmark of PD is the loss of dopaminergic (DA) neurons. Little is known as to why these neurons are vulnerable to PD. We performed a genome-wide screen using over 200 wild-caught Drosophila melanogaster lines from the Drosophila Genetic Reference Panel (DGRP) to identify genes involved in the maintenance of DA neurons. From this screen, we found the gene CG42339. CG42339 is a previously unannotated gene with a human ortholog. Mutations and non-cell autonomous knockdown of CG42339 caused DA neuron loss in the Drosophila brain at late adulthood. We also discovered a progressive locomotor defect in the mutations and knockdown of CG42339. We further examined CG42339 by investigating the mechanistic function this gene plays in the maintenance of DA neurons. We were able to rescue this loss of DA neurons in a CG42339 mutant by limiting the innate immune response and inhibiting nitric oxide signaling. CG42339 appears to be acting as a receptor for advanced glycation end-products (RAGE), therefore we named this gene vexed.