Caspase 3/7 Inhibitors Show Potential for Anti-Inflammatory Therapies

Apoptosis is one of the best-characterized phenomena in cellular and molecular biology. Not only is it essential for successful development, but its deregulation also leads to a number of human diseases, most notably cancer. The cysteine aspartate protease (caspase) family of proteins has been studied extensively over the past several decades and found to play a pivotal role in the execution of apoptosis; caspase activation is regarded as commitment to programmed cell death. A variety of intrinsic and extrinsic stressors are capable of initiating mediated cell death, however, transduction commonly occurs via caspase activity. Initiator caspases (8, 9, 10 and 2) are activated first, generally by binding oligomeric adaptor proteins, and subsequently activate the effector caspases (3, 7 and 6) via proteolytic cleavage.

Recent research has revealed a novel role for caspases, notably caspase-8 and -3/7, in mediating neurotoxicity in response to inflammatory stimuli in microglia. Although microglia are the primary effectors of the immune response in the nervous system, numerous studies suggest that their aberrant activation contributes to neurodegenerative diseases such as Parkinson’s disease, Alzheimer’s and multiple sclerosis. In their groundbreaking research, Burgillos, et al. show that exposure of microglia to pro-inflammatory cytokines leads to activation of caspase-3/7 and neurotoxicity associated with neurological disease. Surprisingly, they also demonstrated that inhibition of caspase-3/7 inhibited microglial activation, and that lipopolysaccharides failed to damage neighboring neurons when caspase-3/7 was abrogated chemically or with siRNA. Finally, they provide evidence that the IKK/NF-kB pathway—a canonical pro-inflammatory pathway-- is also influenced by caspase-3/7 by their ability to trigger PKC-delta.

Neuronal inflammation is both a prominent cause and result of brain injury and the identification of caspase-3/7 and -8 in its etiology provides exciting new targets for potential therapies. Coupled with the advent of nano-carriers capable of traversing the blood brain barrier, caspase-3/7 could be promising substrates for novel anti-inflammatory drugs. Novus Biologicals provides several excellent antibodies to target caspase-3 and -7 (such as NB500-206 and NB500-210) that we hope will accelerate research in this field. We are committed to producing quality research materials, and look forward to learning how our caspase 3 and caspase 7 antibodies will serve the scientific community.

Burgillos MA, Deierborg T, Kavanagh E, et al. Caspase signaling controls microglia activation and neurotoxicity. Nature 2011; 472:319-324.

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