Melatonin, a calpain inhibitor in the central nervous system: Current status and future perspectives

Abstract

Dysregulation of neuronal Ca and oxidative stress plays an important role in the activation of cysteine proteases including calpains and caspases that contribute to neuronal death. In neurodegenerative diseases, traumatic brain injury, stroke, and neuropathic pain calpain activities are markedly increased. Melatonin is a beneficial supplement in the treatment of central nervous system (CNS) disorders. Melatonin is a potent antioxidant and works as a free-radical scavenger to regulate a large number of molecular pathways, including oxidative stress, inflammation, apoptosis, and cell death under different pathological conditions. However, limited studies have evaluated the inhibitory effect of melatonin on calpains. This review summarizes the current knowledge related to the effects of melatonin on calpains in some of the common CNS disorders.

Melatonin receptor-mediated attenuation of excitotoxic cell death in cultured spinal cord slices

“…Oxidative stress and dysregulation of neuronal Ca 2+ play important roles in the activation of calpains and caspases that may contribute to neuronal death (28). Thus, in addition to caspases, calpain and its inhibitor, calpastatin, were also evaluated in LGA/melatonin treated spinal cord slice cultures.…”

Advances in Characterizing Recently-Identified Molecular Actions of Melatonin: Clinical Implications

“…Melatonin also reduces deleterious apoptotic processes in the central nervous system because of its ability to limit the activity of calpains either directly or by increasing the activity of calpastatin, a major inhibitor of calpains [241]. After spinal cord injury, an increased concentration of Ca 2+ induces an activation of the calpains.…”

“…Methamphetamine is a neurotoxic molecule that causes neuronal apoptosis and activates glial cells in the central nervous system. It functions to reduce cell viability by depleting calpastatin levels which upregulate calpains and caspases [241]. Melatonin reverses the depletion of calpastatin and improves mitochondrial dysfunction thereby lowering cell death by reducing apoptosis [234,235].…”

Potential therapeutic role of melatonin in traumatic brain injury: A literature review

“…Melatonin is secreted from the pineal gland by physiological circadian cycles. It has several physiological functions such as mediator of circannual reproductive rhythms (Tamtaji et al 2019). However, it has also a regulatory role in the pathophysiological pathways of traumatic brain injury (TBI) in human and rodents (Barlow et al 2019).…”