Melatoninergic System in Parkinson's Disease: From Neuroprotection to the Management of Motor and Nonmotor Symptoms.
Melatonin is synthesized by several tissues besides the pineal gland, and beyond its regulatory effects in light-dark cycle, melatonin is a hormone with neuroprotective, anti-inflammatory, and antioxidant properties. Melatonin acts as a free-radical scavenger, reducing reactive species and improving mitochondrial homeostasis. Melatonin also regulates the expression of neurotrophins that are involved in the survival of dopaminergic neurons and reducesα-synuclein aggregation, thus protecting the dopaminergic system against damage. The unbalance of pineal melatonin synthesis can predispose the organism to inflammatory and neurodegenerative diseases such as Parkinson's disease (PD). The aim of this review is to summarize the knowledge about the potential role of the melatoninergic system in the pathogenesis and treatment of PD. The literature reviewed here indicates that PD is associated with impaired brain expression of melatonin and its receptors MT1and MT2. Exogenous melatonin treatment presented an outstanding neuroprotective effect in animal models of PD induced by different toxins, such as 6-hydroxydopamine (6-OHDA), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP), rotenone, paraquat, and maneb. Despite the neuroprotective effects and the improvement of motor impairments, melatonin also presents the potential to improve nonmotor symptoms commonly experienced by PD patients such as sleep and anxiety disorders, depression, and memory dysfunction.
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina (UFSC), Campus Universitário, Florianópolis, SC, Brazil.
Josiel Mileno
0000-0001-9993-0774
JM
Mack
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina (UFSC), Campus Universitário, Florianópolis, SC, Brazil.
Marissa Giovanna
MG
Schamne
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina (UFSC), Campus Universitário, Florianópolis, SC, Brazil.
Tuane Bazanella
TB
Sampaio
Queensland Brain Institute, University of Queensland (UQ), Brisbane, QLD, Australia.
Renata Aparecida Nedel
RA
Pértile
Department of Physiology, Institute of Bioscience, University of São Paulo (USP), São Paulo, SP, Brazil.
Pedro Augusto Carlos Magno
PA
Fernandes
Department of Physiology, Institute of Bioscience, University of São Paulo (USP), São Paulo, SP, Brazil.
Regina P
RP
Markus
Department of Pharmacology, Centre of Biological Sciences, Universidade Federal de Santa Catarina (UFSC), Campus Universitário, Florianópolis, SC, Brazil.
Rui Daniel
0000-0002-7547-6463
RD
Prediger
D006801:Humans; D008550:Melatonin / Q000494:pharmacology*; D000066829:Neuroprotection; D010300:Parkinson Disease / Q000235:genetics* / Q000473:pathology
D008550:Melatonin