Calpain-mediated signaling mechanisms in neuronal injury and neurodegeneration

Mol Neurobiol. 2008 Aug;38(1):78-100. doi: 10.1007/s12035-008-8036-x. Epub 2008 Aug 7.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.
  • Review

MeSH terms

  • Alzheimer Disease / pathology
  • Alzheimer Disease / physiopathology
  • Amyotrophic Lateral Sclerosis / pathology
  • Amyotrophic Lateral Sclerosis / physiopathology
  • Animals
  • Brain Ischemia / pathology
  • Brain Ischemia / physiopathology
  • Calpain / chemistry
  • Calpain / genetics
  • Calpain / metabolism*
  • Humans
  • Huntington Disease / pathology
  • Huntington Disease / physiopathology
  • Multiple Sclerosis / pathology
  • Multiple Sclerosis / physiopathology
  • Neurodegenerative Diseases* / pathology
  • Neurodegenerative Diseases* / physiopathology
  • Parkinson Disease / pathology
  • Parkinson Disease / physiopathology
  • Prion Diseases / pathology
  • Prion Diseases / physiopathology
  • Signal Transduction / physiology*
  • Trauma, Nervous System* / pathology
  • Trauma, Nervous System* / physiopathology


  • Calpain