Calpain-1 and Calpain-2 in the Brain: Dr. Jekill and Mr Hyde?

Current Neuropharmacology
Michel Baudry

Abstract

While the calpain system has now been discovered for over 50 years, there is still a paucity of information regarding the organization and functions of the signaling pathways regulated by these proteases, although calpains play critical roles in many cell functions. Moreover, calpain overactivation has been shown to be involved in numerous diseases. Among the 15 calpain isoforms identified, calpain-1 (aka µ-calpain) and calpain-2 (aka m-calpain) are ubiquitously distributed in most tissues and organs, including the brain. We have recently proposed that calpain-1 and calpain- 2 play opposite functions in the brain, with calpain-1 activation being required for triggering synaptic plasticity and neuroprotection (Dr. Jekill), and calpain-2 limiting the extent of plasticity and being neurodegenerative (Mr. Hyde). Calpain-mediated cleavage has been observed in cytoskeleton proteins, membrane-associated proteins, receptors/channels, scaffolding/anchoring proteins, and protein kinases and phosphatases. This review will focus on the signaling pathways related to local protein synthesis, cytoskeleton regulation and neuronal survival/death regulated by calpain-1 and calpain-2, in an attempt to explain the origin of the opposite functions ...Continue Reading

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Citations

Feb 6, 2020·Expert Opinion on Drug Discovery·Levente Endre DókusZoltán Bánóczi
Oct 21, 2020·Bioscience Reports·Fumiko Shinkai-OuchiYasuko Ono
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Jun 8, 2021·Frontiers in Chemistry·Agnieszka StaśkiewiczRafal Latajka
Aug 13, 2021·Scientific Reports·L Rodríguez-FernándezE R García-Trevijano

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