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Caspases (cysteine-aspartic proteases or cysteine-dependent aspartate-directed proteases) are a family of cysteine proteases that play essential roles in apoptosis (programmed cell death), necrosis, and inflammation. Caspases are essential in cells for apoptosis, or programmed cell death, in development and most other stages of adult life, and have been termed "executioner" proteins for their roles in the cell. Some caspases are also required in the immune system for the maturation of lymphocytes. Failure of apoptosis is one of the main contributions to tumour development and autoimmune diseases; this, coupled with the unwanted apoptosis that occurs with ischemia or Alzheimer's disease, has stimulated interest in caspases as potential therapeutic targets since they were discovered in the mid-1990s. ==Types of caspase proteins== , twelve caspases have been identified in humans.〔(HUGO Gene Nomenclature Committee )〕 There are two types of apoptotic caspases: initiator (apical) caspases and effector (executioner) caspases. Initiator caspases (e.g., CASP2, CASP8, CASP9, and CASP10) cleave inactive pro-forms of effector caspases, thereby activating them. Effector caspases (e.g., CASP3, CASP6, CASP7) in turn cleave other protein substrates within the cell, to trigger the apoptotic process. The initiation of this cascade reaction is regulated by caspase inhibitors. CASP4 and CASP5, which are overexpressed in some cases of vitiligo and associated autoimmune diseases caused by NALP1 variants,〔(17377166 )〕 are not currently classified as initiator or effector in (MeSH ),〔(NIH Medical Subject Headings )〕 because they are ''inflammatory'' enzymes that, in concert with CASP1, are involved in T-cell maturation. ==Caspase cascade== Caspases are regulated at a post-translational level, ensuring that they can be rapidly activated. They are first synthesized as inactive ''pro-caspases'', that consist of a prodomain, a small subunit and a large subunit. Initiator caspases possess a longer prodomain than the effector caspases, whose prodomain is very small. The prodomain of the initiator caspases contain domains such as a CARD domain (e.g., caspases-2 and caspase-9) or a death effector domain (DED) (caspases-8 and caspase-10) that enables the caspases to interact with other molecules that regulate their activation. These molecules respond to stimuli that cause the clustering of the initiator caspases. Such clustering allows them to activate automatically, so that they can proceed to activate the effector caspases. The core interaction of caspases may be regarded as a positive feedback. The caspase cascade can be activated by: *granzyme B (released by cytotoxic T lymphocytes and NK cells), which is known to activate caspase-3 and -7 *death receptors (like Fas, TRAIL receptors and TNF receptor), which can activate caspase-8 and -10 *the apoptosome (regulated by cytochrome c and the Bcl-2 family), which activates caspase-9. Some of the final targets of caspases include: *nuclear lamins *ICAD/DFF45 (inhibitor of caspase activated DNase or DNA fragmentation factor 45) *PARP (poly-ADP ribose polymerase) *PAK2 (P 21-activated kinase 2). The role of caspase substrate cleavage in the morphology of apoptosis is not clear. However, ICAD/DFF45 acts to restrain CAD (caspase-activated DNase). The cleavage and inactivation of ICAD/DFF45 by a caspase allows CAD to enter the nucleus and fragment the DNA, causing the characteristic 'DNA ladder' in apoptotic cells. In 2009, Queensland researchers announced caspase 1 and 3 in macrophages are regulated by p202 (a double-stranded DNA binding protein) reducing caspase response, and AIM2 (another double-stranded DNA binding protein) increasing caspase activation.() 抄文引用元・出典: フリー百科事典『 ウィキペディア（Wikipedia）』 ■ウィキペディアで「Caspase」の詳細全文を読む スポンサード リンク
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