PT  - JOURNAL ARTICLE
AU  - Nagarajan, Archana
AU  - Ning, Ye
AU  - Reisner, Kaja
AU  - Buraei, Zafir
AU  - Larsen, Jan Petter
AU  - Hobert, Oliver
AU  - Doitsidou, Maria
TI  - Progressive Degeneration of Dopaminergic Neurons through TRP Channel-Induced Cell Death
AID  - 10.1523/JNEUROSCI.4540-13.2014
DP  - 2014 Apr 23
TA  - The Journal of Neuroscience
PG  - 5738--5746
VI  - 34
IP  - 17
4099  - http://www.jneurosci.org/content/34/17/5738.short
4100  - http://www.jneurosci.org/content/34/17/5738.full
SO  - J. Neurosci.2014 Apr 23; 34
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.