Melatonin as a Neuroprotective Agent in the Rodent Models of Parkinson’s Disease: Is it All Set to Irrefutable Clinical Translation?

Abstract

Parkinson's disease (PD), a neurodegenerative disorder, is characterized by the selective degeneration of the nigrostriatal dopaminergic neurons, continuing or permanent deficiency of dopamine, accretion of an abnormal form of alpha synuclein in the adjacent neurons, and dysregulation of ubiquitin proteasomal system, mitochondrial metabolism, permeability and integrity, and cellular apoptosis resulting in rigidity, bradykinesia, resting tremor, and postural instability. Melatonin, an indoleamine produced almost in all the organisms, has anti-inflammatory, anti-apoptotic, and anti-oxidant nature. Experimental studies employing 1-methyl 4-phenyl 1, 2, 3, 6-tetrahydropyridine (MPTP), 6-hydroxydopamine (6-OHDA), methamphetamine, rotenone, and maneb and paraquat models have shown an enormous potential of melatonin in amelioration of the symptomatic features of PD. Although a few reviews published previously have described the multifaceted efficacy of melatonin against MPTP and 6-OHDA rodent models, due to development and validation of the newer models as well as the extensive studies on the usage of melatonin in entrenched PD models, it is worthwhile to bring up to date note on the usage of melatonin as a neuroprotective agent in PD. This article presents an update on the usage and applications of melatonin in PD models along with incongruous observations. The impending implications in the clinics, success, limitations, and future prospective have also been discussed in this article.

Lithium protects against methamphetamine-induced neurotoxicity in PC12 cells via Akt/GSK3β/mTOR pathway

“…The results indicated that the generation of ROS was increased after MA exposure (Fig. 6C, p < Extensive investigations demonstrate that MA is neurotoxic both in vivo and in vitro [24,25]. Interestingly, Li is found to be neuroprotective both in vivo and in vitro M A N U S C R I P T A C C E P T E D ACCEPTED MANUSCRIPT 11 as well and even could be benefit in treating neurodegenerative diseases, such as Alzheimer's disease [26].…”

Melatonin attenuates MPTP-induced neurotoxicity via preventing CDK5-mediated autophagy and SNCA/α-synuclein aggregation

“…14,31 Melatonin, the main secretory product of the pineal gland, can easily cross the blood-brain barrier and has plentiful neuroprotective properties such as regulating circadian rhythms and providing anti-inflammatory and neuronal protection. [32][33][34] As a naturally occurring compound, melatonin has potential effects on inhibiting autophagy through a redox-mediated scavenge of free radicals and lipid peroxidation, 35 as well as its well-known antioxidant properties. 36 Emerging evidence suggests that melatonin can be used as a neuroprotective agent in the rodent models of PD 32,37,38 by ameliorating the dysfunction of mitochondria, [39][40][41][42] blocking CASP3 (caspase 3, apoptosis-related cysteine peptidase) activation and cellular apoptosis, 43 and protecting TH (tyrosine hydroxylase)-positive nerve terminals.…”

In vitrocultures ofBacopa monnieriand an analysis of selected groups of biologically active metabolites in their biomass

“…Indole compounds are involved in the regulation of sleep, mood; it coordinates the work of the biological clock controlling circadian rhythm, exhibits anticancer properties, and plays a neuroprotective role. Indole derivatives are also compounds with anti-inflammatory and analgesic properties (Wurst et al 2004;Keszthelyi et al 2009;Esposito & Cuzzocrea 2010;Singhal et al 2012). Biological activity of phenolic acids is related to their antioxidant activity that protects the vital structures such as chromosomal DNA, structural proteins, enzymes, and LDL and lipids of cellular membranes from oxidative damage (Yeh et al 2009).…”