State Key Laboratory of Protein and Plant Gene Research and
PubMed | State Key Laboratory of Protein and Plant Gene Research and
Type: | Journal: Annual review of pharmacology and toxicology | Year: 2015
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 Huntingtons disease and Alzheimers 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 Huntingtons disease. Active caspase-6 is present in early stages of Alzheimers disease, and caspase-6 activity is associated with the diseases 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.