SpeedyRINGO inhibits calpain-directed apoptosis in neurons

J Alzheimers Dis. 2012;31(4):779-91. doi: 10.3233/JAD-2012-120652.


The calcium-activated proteolytic enzyme calpain is one of the key proteins that can directly or indirectly drive neurons into apoptosis. The indirect way is through cyclin dependent kinase 5 (CDK5), a non-mitotic kinase, which is upregulated through calpain overactivation and followed by a subsequent increase in p53 and active caspase-3 levels under neurodegenerative conditions. The direct way is the upregulation of p53 by calpain itself, since p53 is a substrate for it. SpeedyRINGO is an atypical cell cycle regulator that has been shown to have protective effects in mitotic cells against apoptosis by inhibiting caspase-3 activation when p53 is present. Our aim was to reveal possible protective effects of SpeedyRINGO against calpain-induced caspase-3 activation in neurons which is crucial in terms of providing novel insights in preventing the caspase-3 activation cascade in neurodegeneration. For this reason, mRNA and protein levels were analyzed by qRT-PCR, western blotting, and immunofluorescence. We show that calpain overactivation leads to the upregulation of p53 and a subsequent increase in active caspase-3 level, indicating activation of apoptotic machinery in neurons. This calpain-directed caspase-3 activation upon upregulation of p53 is inhibited by the expression of SpeedyRINGO in rat hippocampal neurons. Therefore, SpeedyRINGO acts as a savior for neurons that are under apoptosis due to caspase-3 activation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Animals, Newborn
  • Apoptosis / physiology*
  • Apoptosis Regulatory Proteins / physiology*
  • Calpain / antagonists & inhibitors*
  • Calpain / physiology*
  • Cell Cycle Proteins / physiology*
  • Cell Differentiation / physiology
  • Cells, Cultured
  • Hippocampus / cytology
  • Hippocampus / metabolism
  • Neurons / cytology
  • Neurons / metabolism*
  • Rats
  • Rats, Sprague-Dawley


  • Apoptosis Regulatory Proteins
  • Cell Cycle Proteins
  • SPDYA protein, human
  • Calpain