RT Journal Article SR Electronic T1 Progressive Degeneration of Dopaminergic Neurons through TRP Channel-Induced Cell Death JF The Journal of Neuroscience JO J. Neurosci. FD Society for Neuroscience SP 5738 OP 5746 DO 10.1523/JNEUROSCI.4540-13.2014 VO 34 IS 17 A1 Archana Nagarajan A1 Ye Ning A1 Kaja Reisner A1 Zafir Buraei A1 Jan Petter Larsen A1 Oliver Hobert A1 Maria Doitsidou YR 2014 UL http://www.jneurosci.org/content/34/17/5738.abstract AB 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.