Abstract
This article discusses the role that melatonin may have in the prevention and treatment of Parkinson’s disease (PD). In parkinsonian patients circulating melatonin levels are consistently disrupted and the potential therapeutic value of melatonin on sleep disorders in PD was examined in a limited number of clinical studies using 2–5 mg/day melatonin at bedtime. The low levels of melatonin MT1 and MT2 receptor density in substantia nigra and amygdala found in PD patients supported the hypothesis that the altered sleep/wake cycle seen in PD could be due to a disrupted melatonergic system. Motor symptomatology is seen in PD patients when about 75% of the dopaminergic cells in the substantia nigra pars compacta region degenerate. Nevertheless, symptoms like rapid eye movement (REM) sleep behavior disorder (RBD), hyposmia or depression may precede the onset of motor symptoms in PD for years and are index of worse prognosis. Indeed, RBD patients may evolve to an α-synucleinopathy within 10 years of RBD onset. Daily bedtime administration of 3–12 mg of melatonin has been demonstrated effective in RDB treatment and may halt neurodegeneration to PD. In studies on animal models of PD melatonin was effective to curtail symptomatology in doses that allometrically projected to humans were in the 40–100 mg/day range, rarely employed clinically. Therefore, double-blind, placebo-controlled clinical studies are urgently needed in this respect.
Highlights
With a prevalence of 1–4% in people >60 years of age, Parkinson’s disease (PD) is the second most common neurodegenerative disorder (Tysnes and Storstein, 2017)
This review focuses on the effects of melatonin on neurodegeneration in animal models of PD in relation to the possible human doses to be employed
Due to the hypnotic and chronobiotic properties of melatonin, its use for the treatment of insomnia has been recommended. Several metaanalyses support such a therapeutic role (Auld et al, 2017; FerracioliOda et al, 2018; Li et al, 2019) a number of consensuses concluded that melatonin is the first-line treatment when a hypnotic is indicated in patients over 55 years of age (Wilson et al, 2010; Geoffroy et al, 2019; Palagini et al, 2020; Vecchierini et al, 2020)
Summary
With a prevalence of 1–4% in people >60 years of age, Parkinson’s disease (PD) is the second most common neurodegenerative disorder (Tysnes and Storstein, 2017). Administration to rats placed in L:D 12:12 of rotenone, a pesticide with toxic effects in dopaminergic neurons, produced a reduction in the mean value and amplitude of the circadian locomotor activity and body temperature rhythms (Lax et al, 2012). Other signaling pathways include up-regulation of nuclear factor erythroid 2-related factor 2 and of toll-like receptor-4 activation and high-mobility group box-1 signaling receptors, and prevention of NLRP3 inflammasome activation by melatonin (Hardeland et al, 2011) These effects of melatonin result in increased production of anti-inflammatory cytokines and reduced levels of pro-inflammatory cytokines (Carrillo-Vico et al, 2013; Hardeland, 2018a). Regardless of the discrepancies cited, the preventive activity of melatonin in neurodegeneration related to PD is generally accepted (Lin et al, 2007; Chang et al, 2012; Leeboonngam et al, 2018)
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