Referenced in: none

Automatically associated channels: TRP

Title: Progressive degeneration of dopaminergic neurons through TRP channel-induced cell death.

Authors: Archana Nagarajan, Ye Ning, Kaja Reisner, Zafir Buraei, Jan Petter Larsen, Oliver Hobert, Maria Doitsidou

Journal, date & volume: J. Neurosci., 2014 Apr 23 , 34, 5738-46

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/24760834

Abstract
Progressive neurodegenerative diseases are among the most frequently occurring aging-associated human pathologies. In a screen for Caenorhabditis elegans mutant animals that lack their normal complement of dopaminergic neurons, we identified two strains with progressive loss of dopaminergic neurons during postembryonic life. Through whole-genome sequencing we show that both strains harbor dominant (d), gain-of-function mutations in the Transient Receptor Potential (TRP) mechanosensory channel trp-4, a member of the invertebrate and vertebrate TRPN-type of the TRP family channels. Gain-of-function mutations in TRP channels have not been previously implicated in dopaminergic neuronal degeneration. We show that trp-4(d) induces cell death in dopamine neurons through a defined, calcium-related downstream pathway.