Clarification of roles of calcium-dependent cytosolic protease calpain on neuronal cell death

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In this study, I investigated possible involvement of calpain. Using gene-engineering techniques, I generated calpain activity-augmented and suppressed model mice, and clarified that calpain activation caused exacerbation of Aβamyloidosis, tau phosphorylation, microgliosis, somato-dendritic dystrophy and mortality. In addition, I found that vesicular GABA transporter (VGAT) is cleaved by calpain after excitotoxic stimulation or a cerebral ischemia model. These observations indicate that calpain activation may underlie Aβ-triggered pathological cascade and thus shall become a relevant pharmacological target in the treatment of AD.