Accordingly, the demonstration that GSH depletion in glial cells promotes neuroinflammation through a mechanism involving TRPM2 [31], paired with our demonstration that GSH depletion facilitates TRPM2 function in vulnerable hippocampal pyramidal neurons, suggests that TRPM2 activation contributes to neuronal demise in neurodegenerative disease through multiple mechanisms. This evidence concerns the gene TRPM2 and neurodegenerative disease.