TRPM7 Channels as Therapeutic Targets for Neuroprotection

Transient receptor potential melastatin 7 （TRPM7） channel is a member of TRP superfamily and a calci- um-permeable non-selective cation channel. TRPM7 channel is a non-glutamate mechanism that mediates ischemic brain damage in stroke. TRPM7 is ubiquitously expressed in many cells and tissues including brain. Its function is not yet fully studied because there is no selective pharmacological antagonist and a global knockout of TRPM7 chan- nel is embryonic lethal. TRPM7 has been previously showed to play a key role in hypoxic neuronal cell death in- vitro using siRNA. We have demonstrated that suppression of TRPM7 using virally mediated gene silencing in adult rat brain reduced subsequent neuronal cell death after cerebral ischemia and preserved behavioural and functional outcomes （including long-term potentiation （LTP）, fear-associated and spatial-navigational memory tasks） follow- ing the stroke. This serves as proof of principle study. Thus, TRPM7 is a potential therapeutic target for drug de- velopment in stroke.