Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration

P. S. Vosler, C. S. Brennan, J. Chen

Research output: Contribution to journalReview articlepeer-review

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.

Original languageEnglish (US)
Pages (from-to)78-100
Number of pages23
JournalMolecular Neurobiology
Volume38
Issue number1
DOIs
StatePublished - Aug 2008
Externally publishedYes

Keywords

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

ASJC Scopus subject areas

  • Neurology
  • Cellular and Molecular Neuroscience

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