Reaction: Calpain cleaves p35 to p25
- in pathway: Deregulated CDK5 triggers multiple neurodegenerative pathways in Alzheimer's disease models
A variety of neurotoxic insults such as beta-amyloid (A-beta), ischemia, excitotoxicity and oxidative stress disrupt the intracellular calcium homeostasis in neurons, thereby leading to the activation of calpain, which cleaves p35 into p25 and p10 (Lee et al. 2000). p25 has a six-fold longer half-life compared to p35 and lacks the membrane anchoring signal, which results in its constitutive activation and mislocalization of the CDK5:p25 complex to the cytoplasm and the nucleus.
Calpain-mediated cleavage of p35 to p25 is inhibited by calpastatin (CAST). CAST levels are decreased in Alzheimer disease (Sato et al. 2011).
Reaction - small molecule participants:
H2O [cytosol]
Reactome.org reaction link: R-HSA-8863012
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Reaction input - small molecules:
water
Reaction output - small molecules:
Reactome.org link: R-HSA-8863012