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Calpain-Mediated Signaling Mechanisms in Neuronal Injury and Neurodegeneration

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Abstract

Calpain is a ubiquitous calcium-sensitive protease that is essential for normal physiologic neuronal function. However, alterations in calcium homeostasis lead to persistent, pathologic activation of calpain in a number of neurodegenerative diseases. Pathologic activation of calpain results in the cleavage of a number of neuronal substrates that negatively affect neuronal structure and function, leading to inhibition of essential neuronal survival mechanisms. In this review, we examine the mechanistic underpinnings of calcium dysregulation resulting in calpain activation in the acute neurodegenerative diseases such as cerebral ischemia and in the chronic neurodegenerative diseases including Alzheimer’s disease, Parkinson’s disease, Huntington’s disease, multiple sclerosis, prion-related encephalopathy, and amylotrophic lateral sclerosis. The premise of this paper is that analysis of the signaling and transcriptional consequences of calpain-mediated cleavage of its various substrates for any neurodegenerative disease can be extrapolated to all of the neurodegenerative diseases vulnerable to calcium dysregulation.

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Correspondence to J. Chen.

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This work was supported by NIH/NINDS grants (NS43802, NS45048, NS44178, NS 56118, and NS36736) and VA Merit Review to J.C. Additional support was provided by the American Heart Association to P.V. (0715254U). We thank Armando P. Signore for editorial assistance and Pat Strickler for secretarial support.

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Vosler, P.S., Brennan, C.S. & Chen, J. Calpain-Mediated Signaling Mechanisms in Neuronal Injury and Neurodegeneration. Mol Neurobiol 38, 78–100 (2008). https://doi.org/10.1007/s12035-008-8036-x

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  • DOI: https://doi.org/10.1007/s12035-008-8036-x

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