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Role of melatonin in neurodegenerative diseases

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Abstract

The pineal product melatonin has remarkable antioxidant properties. It scavenges hydroxyl, carbonate and various organic radicals, peroxynitrite and other reactive nitrogen species. Melatonyl radicals formed by scavenging combine with and, thereby, detoxify superoxide anions in processes terminating the radical reaction chains. Melatonin also enhances the antioxidant potential of the cell by stimulating the synthesis of antioxidant enzymes like superoxide dismutase, glutathione peroxidase and glutathione reductase, and by augmenting glutathione levels. The decline in melatonin production in aged individuals has been suggested as one of the primary contributing factors for the development of age-associated neurodegenerative diseases,e.g., Alzheimer’s disease. Melatonin has been shown to be effective in arresting neurodegenerative phenomena seen in experimental models of Alzheimer’s disease, Parkinsonism and ischemic stroke. Melatonin preserves mitochondrial homeostasis, reduces free radical generation, e.g., by enhancing mitochondrial glutathione levels, and safeguards proton potential and ATP synthesis by stimulating complex I and IV activities. Therapeutic trials with melatonin have been effective in slowing the progression of Alzheimer’s disease but not of Parkinson’s disease. Melatonin’s efficacy in combating free radical damage in the brain suggests that it may be a valuable therapeutic agent in the treatment of cerebral edema after traumatic brain injury.

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Abbreviations

6-OHDA:

6-hydroxydopamine

AD:

Alzheimer’s disease

AFMK:

N1-acetyl-N2-formyl-5-methoxykynuramine

AMK:

N1-acetyl-5-methoxykynuramine

apoE4:

apolipoprotein E4

Aβ:

amyloid beta

BBB:

blood brain barrier

Bcl-2:

B cell lymphoma proto-oncogene protein

c3OHM:

cyclic 3-hydroxymelatonin

CSF:

cerebrospinal fluid

DA:

dopamine

ETC:

electron transport chain

GPx:

glutathione peroxidase

GR:

glutathione reductase

GSH:

glutathione

GSK-3:

glycogen synthase kinase 3

HIOMT:

hydroxyindole-O-methyl transferase

IL:

Interleukin

iNOS:

inducible NOS

KA:

Kainic acid

MAO:

monoamine oxidase

MAP:

microtubule-associated protein

MDA:

malondialdehyde

MnSOD:

SOD subform with manganese in the active center

MPP+ :

methyl 1–4 phenyl pyridinium

MPTP:

1-methyl-4-phenyl-1,2,3,6 tetrahydropyridine

mtNOS:

mitochondrial nitric oxide synthase

mtPTP:

mitochondrial permeability transition pore mitochondrial permeability transition pore

nNOS:

neuronal NOS

NOS:

nitric oxide synthase

QR2:

quinone reductase

RNS:

reactive nitrogen species

ROS:

reactive oxygen species

SCN:

suprachiasmatic nuclei

SNAT:

serotoninN-acetyltransferase

SOD:

superoxide dismutase

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Authors and Affiliations

  1. Department of Physiology, Pusat Pengajian Sains Perubatan, School of Medical Sciences, Universiti Sains Malaysia, Kampus Kesihatan, 16150, Kubang Kerian, Kelantan, Malaysia

    V. Srinivasan

  2. Section of Sleep Medicine, Department of Neurology, SUNY Downstate Medical Center, 11203, Brooklyn, NY, USA

    S. R. Pandi-Perumal

  3. Istituto Cantonale di Patologia, 6601, Locarno, Switzerland

    G. J. M. Maestroni

  4. Departamento de Bioquímica y Biología Molecular III, Facultad de Medicina, Universidad Complutense, 28040, Madrid, Spain

    A. I. Esquifino

  5. Institut fur Zoologie und Anthropologie, Universitat Gottingen, D-37073, Gottingen, Germany

    R. Hardeland

  6. Departmento de Fisiología, Facultad de Medicina, Universidad de Buenos Aires, 1121, Buenos Aires, Argentina

    D. P. Cardinali

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  1. V. Srinivasan
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  6. D. P. Cardinali
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Srinivasan, V., Pandi-Perumal, S.R., Maestroni, G.J.M. et al. Role of melatonin in neurodegenerative diseases. neurotox res 7, 293–318 (2005). https://doi.org/10.1007/BF03033887

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