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Cysteine Proteases, Synaptic Degeneration and Neuroodegenerative Disorders

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Role of Proteases in the Pathophysiology of Neurodegenerative Diseases

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Conclusions

Caspases and calpains act on many different protein substrates in neurons, and cleavage of these substrates results in a variety of physiological and pathophysiological changes in the structure and function of neuronal circuits. In addition to playing central roles in the process of neuronal apoptosis, caspases appear to regulate synaptic plasticity and may be involved in synaptic degeneration and remodeling. The calcium sensitivity of calpains suggests that they are important effectors of changes in neurons brought about by calcium influx, an important physiological and pathological signal in neurons. Many different neurodegenerative disorders involve excessive activation of caspases and calpains including Alzheimer’s, Parkinson’s, Huntington’s diseases and stroke. Experimental findings suggest that caspase and/or calpain inhibitors can attenuate neuronal degeneration in models of these neurodegenerative disorders.

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Authors and Affiliations

  1. Laboratory of Neurosciences, National Institute on Aging, Baltimore, MD, 21224

    Mark P. Mattson & Sic L. Chan

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  1. Mark P. Mattson
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  1. Nathan S. Kline Institute for Psychiatric Research, Orangeburg, New York

    Abel Lajtha

  2. Medical University of South Carolina, Charleston, South Carolina

    Naren L. Banik

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Mattson, M.P., Chan, S.L. (2002). Cysteine Proteases, Synaptic Degeneration and Neuroodegenerative Disorders. In: Lajtha, A., Banik, N.L. (eds) Role of Proteases in the Pathophysiology of Neurodegenerative Diseases. Springer, Boston, MA. https://doi.org/10.1007/0-306-46847-6_9

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  • DOI: https://doi.org/10.1007/0-306-46847-6_9

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