TRPC channels and programmed cell death

Abstract

Neurotrophins, including nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF), bind to their high-affinity receptors to promote neuronal survival during brain development. One of the key downstream pathways is the phospholipase C (PLC) pathway, which not only plays a central role in calcium release from internal store but also in activation of TRPC channels coupled with neurotrophin receptors. TRPC channels are required for the neurotrophin-mediated neuronal protective effects. In addition, activation of TRPC channels is able to protect neurons in the absence of neurotrophin. In some circumstances, TRPC channels coupled with metabotropic glutamate receptor may mediate the excitotoxicity by calcium overload. One of the key questions in the field is the channel gating mechanisms; understanding of which would help design compounds to modulate the channel properties. The development and identification of TRPC channel agonists or blockers are promising and may unveil new therapeutic drugs for the treatment of neurodegenerative diseases and epilepsy.