Based on the data obtained in a series of experiments with laboratory animals, conclusions about changes in the activity of calcium-dependent proteases in the brains of rats with induced neurodegeneration have been drawn. The properties of the proteolytic and regulatory components of the calpain system under the action of neurotoxic agents: amyloid β-peptide and glutamate have been characterized, and the main endogenous regulatory mechanisms of changes in the intensity of calcium-dependent proteolysis have been established. The neuroprotective properties of exogenous calpain regulators acting by different mechanisms: sex steroids and calcium channel regulators have been tested on degeneration models examined.