Involvement of Caspases in the Pathophysiology of Neurodegeneration and Stroke
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
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Involvement of Caspases in the Pathophysiology of Neurodegeneration and Stroke Alakananda Goswami, Prosenjit Sen, Kuladip Jana, and Sanghamitra Raha
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
A. Goswami Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata 700064, West Bengal, India Presently: SN Surgicare & Healthcare Science Private Limited (Associated Company of NSIC, Govt. of India enterprise), Barasat, Kolkata 700121, West Bengal, India P. Sen Department of Biological Chemistry, Indian Association for the Cultivation of Science, Kolkata 700032, West Bengal, India K. Jana Department of Molecular Medicine, Bose Institute, Centenary Campus, Kolkata 700054, West Bengal, India S. Raha (*) Crystallography & Molecular Biology Division, Saha Institute of Nuclear Physics, Kolkata 700064, West Bengal, India Department of Biotechnology, Visva Bharati University, Shantiniketan 731235, West Bengal, India e-mail: [email protected]; [email protected] N.S. Dhalla and S. Chakraborti (eds.), Role of Proteases in Cellular Dysfunction, Advances in Biochemistry in Health and Disease 8, DOI 10.1007/978-1-4614-9099-9_3, © Springer Science+Business Media New York 2014
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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. Keywords Stroke • Parkinson’s disease • Alzheimer’s disease • Caspase • Apoptosis
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Introduction
Knowledge of two fundamental types of cell death, apoptosis and necrosis, has existed since long ago [1]. Cell
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