Caspase-6 and neurodegeneration.
Caspases are cysteine-aspartic proteases that post-translationally modify their substrates through cleavage at specific sites, which causes either substrate inactivation or a gain of function through the generation of active fragments. Currently, each caspase is categorized as either an initiator of apoptosis or an end-stage executioner. Caspase-6 was originally identified as an executioner caspase owing to its role in cleavage of nuclear lamins. However, it has since been shown that caspase-6 cleaves caspases-2, 3 and 8. Furthermore, active caspase-6 is present in post mortem brains of Huntington and Alzheimer disease subjects that do not yet display apoptotic morphology, which suggests a function distinct from its well-validated executioner role. In this review, we discuss evidence to date regarding the role of caspase-6 in neurodegeneration. The findings suggest that selective inhibitors of caspase-6 may have therapeutic potential for various neurodegenerative disorders.
Centre for Molecular Medicine and Therapeutics, Child and Family Research Institute, Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada V5Z 4H4.
Rona K
RK
Graham
Dagmar E
DE
Ehrnhoefer
Michael R
MR
Hayden
D000544:Alzheimer Disease / Q000201:enzymology / Q000473:pathology; D000818:Animals; D053178:Caspase 6 / Q000737:chemistry / Q000378:metabolism*; D061945:Caspase Inhibitors; D004195:Disease Models, Animal; D004789:Enzyme Activation; D006801:Humans; D006816:Huntington Disease / Q000201:enzymology / Q000473:pathology; D008958:Models, Molecular; D009410:Nerve Degeneration / Q000201:enzymology* / Q000473:pathology*; D011487:Protein Conformation
D061945:Caspase Inhibitors; D053178:Caspase 6