Involvement of caspases in the pathophysiology of neurodegeneration and stroke

Abstract

A family of proteases known as caspases is a key element in the proteolytic machinery involved in apoptosis or programmed cell death. Apart from their involvement in cell death, caspases are also associated with the developmental process and other normal functions of adult organisms. Caspases are named such because they constitute a family of cysteine proteases which always cleave an Asp residue in their substrates. Stroke results from a rapid malfunctioning of the brain due to lack of blood supply and is a major health threat producing mortality and morbidity. Majority of strokes are ischemic (80 % of all strokes) and the rest are hemorrhagic. Both forms of divergent cell death mechanisms, necrosis, and apoptosis are observed at different spatial region of ischemic attack. Involvement of multiple caspases in stroke has been documented with caspases 1, 3, 8, 9, and 11 playing major roles. Many neurodegenerative diseases result from loss of functional neurons from the brain through enhanced death of neurons. Neurodegenerative diseases are usually late onset and progressive. Among the most common neurodegenerative disorders in aging populations worldwide, Alzheimer's disease (AD) and Parkinson's disease (PD) definitely warrant mentioning. Abnormal protein deposits in specific regions of the brain give rise to both these diseases triggering reactive oxygen species formation and mitochondrial dysfunction. Caspases are activated by these changes resulting in loss of neurons through cell death. In this review we provide a brief overview of the involvement of caspases in diseases associated with the impairment of brain function.