Neuroprotective strategies against calpain-mediated neurodegeneration

Abstract

Calpains are calcium-dependent proteolytic enzymes that have deleterious effects on neurons upon their pathological over-activation. According to the results of numerous studies to date, there is no doubt that abnormal calpain activation triggers activation and progression of apoptotic processes in neurodegeneration, leading to neuronal death. Thus, it is very crucial to unravel all the aspects of calpain-mediated neurodegeneration in order to protect neurons through eliminating or at least minimizing its lethal effects. Protecting neurons against calpain-activated apoptosis basically requires developing effective, reliable, and most importantly, therapeutically applicable approaches to succeed. From this aspect, the most significant studies focusing on preventing calpain-mediated neurodegeneration include blocking the N-methyl-d-aspartate (NMDA)-type glutamate receptor activities, which are closely related to calpain activation; directly inhibiting calpain itself via intrinsic or synthetic calpain inhibitors, or inhibiting its downstream processes; and utilizing the neuroprotectant steroid hormone estrogen and its receptors. In this review, the most remarkable neuroprotective strategies for calpain-mediated neurodegeneration are categorized and summarized with respect to their advantages and disadvantages over one another, in terms of their efficiency and applicability as a therapeutic regimen in the treatment of neurodegenerative diseases.

Calpastatin peptide attenuates early brain injury following experimental subarachnoid hemorrhage

“…Under physiological conditions, calpain 1 and 2 are involved in neural development, degeneration and synaptic plasticity. However, calcium overloading induces the activation of calpain 1 and 2, which has a deleterious effect on the brain (14,24). Previous studies have revealed that glutamate neurotoxicity is observed in EBI following experimental SAH (11,(25)(26)(27)(28), and that it causes an increase in the intracellular calcium concentration, predominantly through the N-methyl-D-aspartate receptor and the metabotropic glutamate receptor 1 (28), resulting in calpain activation.…”

Natural Products and Their Bioactive Compounds: Neuroprotective Potentials against Neurodegenerative Diseases

“…Neurodegeneration is the progressive dysfunction and loss of neuronal structure and function that resulted in neuronal cell death [1,2]. Neurodegeneration occurs in various diseases affecting the central nervous system (CNS).…”

Calcium-Involved Action of Phytochemicals: Carotenoids and Monoterpenes in the Brain

“…While they remain inactivated in the absence of Ca 2+ , elevation of intracellular calcium levels results in calpain overactivation and, thus, detrimental effects on neurons: abnormally high activity promotes apoptotic processes, neurodegeneration, and, ultimately, neuronal death [42]. In vitro studies indicate that astaxanthin protects porcine lens proteins from hydrolysis by calpains; the results suggest that this carotenoid reacts with calcium ions, decreases the free Ca 2+ level, and thus mitigates the probability of calpain activation [34,43].…”