title: Activation and regulation of caspase-6 and its role in neurodegenerative diseases.
abstract: Caspases, a family of cysteine proteases, are major mediators of apoptosis and inflammation. Caspase-6 is classified as an apoptotic effector, and it mediates nuclear shrinkage during apoptosis, but it possesses unique activation and regulation mechanisms that differ from those of other effector caspases. Furthermore, increasing evidence has shown that caspase-6 is highly involved in axon degeneration and neurodegenerative diseases, such as Huntington's disease and Alzheimer's disease. Cleavage at the caspase-6 site in mutated huntingtin protein is a prerequisite for the development of the characteristic behavioral and neuropathological features of Huntington's disease. Active caspase-6 is present in early stages of Alzheimer's disease, and caspase-6 activity is associated with the disease's pathological lesions. In this review, we discuss the evidence relevant to the role of caspase-6 in neurodegenerative diseases and summarize its activation and regulation mechanisms. In doing so, we provide new insight about potential therapeutic approaches that incorporate the modulation of caspase-6 function for the treatment of neurodegenerative diseases.
authors.affiliation: State Key Laboratory of Protein and Plant Gene Research and.
authors.forename: Xiao-Jun
authors.initials: XJ
authors.lastname: Wang
authors.forename: Qin
authors.initials: Q
authors.lastname: Cao
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Xiao-Dong
authors.initials: XD
authors.lastname: Su
mesh_terms: D000544:Alzheimer Disease / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D000595:Amino Acid Sequence; D016564:Amyloid beta-Protein Precursor / Q000378:metabolism; D000818:Animals; D001921:Brain / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D053178:Caspase 6 / Q000737:chemistry / Q000378:metabolism*; D061945:Caspase Inhibitors / Q000627:therapeutic use; D015195:Drug Design; D004789:Enzyme Activation; D006801:Humans; D000071058:Huntingtin Protein; D006816:Huntington Disease / Q000188:drug therapy / Q000201:enzymology* / Q000473:pathology; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009419:Nerve Tissue Proteins / Q000378:metabolism; D011487:Protein Conformation; D015398:Signal Transduction; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
chemical_list: D016564:Amyloid beta-Protein Precursor; D061945:Caspase Inhibitors; C086055:HTT protein, human; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D053178:Caspase 6
keywords: Alzheimer's disease; Huntington's disease; caspase-6; neurodegeneration; regulation mechanism