Three distinct signaling pathways lead to programmed cell death (apoptosis). The death receptor and mitochondrion pathways are the mains, in which the key apoptotic proteases capase-8 and caspase-9, respectively, are involved. The endoplasmic reticulum (ER) stress is the third apoptotic pathway and caspase-12 is involved (1,2). Caspase-12 is localized to the ER but not to cytoplasm or mitochondrion. Caspase-12 is activated by ER stress, including disruption of ER calcium homeostasis, and mediates ER stress-induced apoptosis. Caspase-12 is co-localized to the ER with several proteins that are involved in AlzheimerÕs disease including -secretase presenilin and -amyloid precursor protein (APP). Caspase-12 mediates cytotoxicity induced by amyloid- . Caspase-12 is ubiquitously expressed in mouse tissues (1).
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