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

在这项研究中，我调查了钙蛋白酶的可能参与。利用基因工程技术，我生成了calpain活性增强和抑制的模型小鼠，并阐明了calpain激活会导致a β淀粉样变性、tau磷酸化、小胶质细胞增生、躯体-树突状营养不良和死亡的加剧。此外，我发现在兴奋毒性刺激或脑缺血模型后，囊泡GABA转运蛋白（VGAT）被钙蛋白酶裂解。这些观察结果表明，钙蛋白酶激活可能是a β触发的病理级联的基础，因此应成为治疗AD的相关药理靶点。

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.