Proteases and Pathological Neurodegeneration
An understanding of the biochemical processes that lead to neuronal damage is crucial to the development of therapies aimed at slowing the progression of neurodegenerative diseases. While brain proteases have long been recognized for their importance to neuropeptide metabolism and protein turnover (Loh et al., 1984; Pope and Nixon, 1984), it is becoming increasingly clear that proteolysis plays a role in pathological neuronal degeneration as well. This chapter briefly reviews the evidence relating proteolytic mechanisms to the neurodegeneration triggered by injury or disease. The focus is on a calcium-dependent protease, calpain 1, and its possible involvement in mediating structural damage produced by excessive accumulation of intracellular free calcium. Because the role of calpain 1 in neurodegenerative processes has been the subject of recent review (Seubert and Lynch, 1990; Siman, 1990; 1992), the present brief review is followed by a description of new studies directed at the localization, timing, and mode of activation of calpain 1 in animal models of neuronal damage.
KeywordsExcitatory Amino Acid Carotid Artery Occlusion Pathological Neurodegeneration Transient Global Ischemia Transient Global Cerebral Ischemia
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