TRPM7-associated Mg2+-inhibited cation channel activity plays a role in neurodegenerative variations associated with Alzheimer's disease (AD) [118]; in AD, presenilin-2 negatively influences the TRPC6-dependent calcium entry [119] and inhibition of TRPM2 by siRNA reduces amyloid-β toxicity, suggesting a role for TRPM2 in neuronal cell death [120]. Here, TRPM2 is linked to early-onset autosomal dominant Alzheimer disease.