The Ca²⁺-Regulated Enzymes Calpain and Calcineurin in Neurodegenerative Processes and Prospects for Neuroprotective Pharmacotherapy

Calcium (Ca²⁺) and the Ca²⁺-regulated enzymes calpain and calcineurin are key molecules in signaling mechanisms in neurons and ensure the normal course of intracellular neurochemical and neurophysiological processes. Imbalances and increases in intracellular Ca²⁺ levels correlate with activation of calpain and calcineurin. Inactivation of endogenous inhibitors and/or the absence of exogenous pharmacological inhibitors of these enzymes creates conditions in which intracellular mechanisms detrimental to neurons are stimulated. The interrelated processes of Ca²⁺ imbalance and calpain and calcineurin deregulation are directly related to the development of intracellular pathophysiological reactions leading to the death of particular neuron populations in neurodegenerative diseases such as Alzheimer’s and Parkinson’s diseases. Thus review describes the characteristics of calpain and calcineurin and discusses their interconnected roles in the neurodegenerative processes. Data on effective actions of exogenous inhibitors (in vivo, in vitro) show that the pharmacological regulation of calpain and calcineurin has promise for neuroprotection.