Molecular Neurobiology

, Volume 38, Issue 1, pp 78–100

Calpain-Mediated Signaling Mechanisms in Neuronal Injury and Neurodegeneration


DOI: 10.1007/s12035-008-8036-x

Cite this article as:
Vosler, P.S., Brennan, C.S. & Chen, J. Mol Neurobiol (2008) 38: 78. doi:10.1007/s12035-008-8036-x


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.


Neurodegenerative disease Calpain Cerebral ischemia Alzheimer’s Parkinson’s Huntington’s Amylotrophic lateral sclerosis Multiple sclerosis Prion-related encephalopathy Excitotoxicity Calcium 

Copyright information

© Humana Press Inc. 2008

Authors and Affiliations

  1. 1.Department of NeurologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  2. 2.Department of PharmacologyUniversity of Pittsburgh School of MedicinePittsburghUSA
  3. 3.Geriatric Research, Educational and Clinical CenterVeterans Affairs Pittsburgh Health Care SystemPittsburghUSA
  4. 4.Center for Neuroscience University of PittsburghPittsburghUSA

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