[Ca2+-regulated enzymes calpain and calcineurin in neurodegenerative processes and prospects for neuroprotective pharmacotherapy].

Abstract

Calcium (Ca²⁺) and Ca²⁺-regulated enzymes calpain and calcineurin are the key molecules of signaling mechanisms in neurons and ensure the normal course of intracellular neurochemical and neurophysiological processes. The imbalance and increase in the intracellular level of Ca²⁺ correlates with the activation of calpain and calcineurin. Inactivation of endogenous inhibitors and/or absence of exogenous pharmacological inhibitors of these enzymes may induce a cascade of intracellular mechanisms that are detrimental to the structural integrity and functional activity of neurons. The interrelated processes of Ca²⁺ imbalance, dysregulation of calpain and calcineurin are directly related to the development of intracellular pathophysiological reactions leading to the degeneration and death of selective neuronal populations in neurodegenerative diseases such as Alzheimer's disease and Parkinson's disease. The review briefly presents the characteristics of calpain and calcineurin, their interrelated role in the neurodegeneration processes. Data on the efficiency of the exogenous inhibitors (in vivo, in vitro) point out the potential role of pharmacological regulation of calpain and calcineurin for neuroprotection.