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Therapeutical Implications of Melatonin in Alzheimer’s and Parkinson’s Diseases

  • Chapter
Tryptophan Metabolism: Implications for Biological Processes, Health and Disease

Part of the book series: Molecular and Integrative Toxicology ((MOLECUL))

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Abstract

Neurodegenerative diseases like Alzheimer’s disease (AD) and Parkinson’s disease (PD) are major health problems, and a growing recognition exists that efforts to prevent them must be undertaken by both governmental and nongovernmental organizations. In this context, the pineal product melatonin has a promising significance because of its chronobiotic/cytoprotective properties. One of the features of advancing age is the gradual decrease in endogenous melatonin synthesis. A limited number of therapeutic trials have indicated that melatonin has a potential therapeutic value as a neuroprotective drug in the treatment of AD, minimal cognitive impairment (which may evolve to AD), and PD. Both in vitro and in vivo, melatonin prevented the neurodegeneration seen in experimental models of AD and PD. For these effects to occur, doses of melatonin about two orders of magnitude higher than those required to affect sleep and circadian rhythmicity are needed. More recently, attention has been focused on the development of potent melatonin analogs with prolonged effects which were employed in clinical trials in sleep-disturbed or depressed patients in doses considerably higher than those employed for melatonin. In view that the relative potencies of the analogs are higher than that of the natural compound, clinical trials employing melatonin in the range of 50–100 mg/day are needed to assess its therapeutic validity in neurodegenerative disorders.

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Abbreviations

6-OHDA:

6-hydroxydopamine

Ach:

Acetylcholine

AChE:

Acetylcholinesterase

AD:

Alzheimer’s disease

AFMK:

N 1-Acetyl-N 2-formyl-5-methoxykynuramine

AMK:

N 1-Acetyl-5-methoxykynuramine

APP:

Amyloid precursor protein

Aβ:

Aggregated β-amyloid

Bcl-2:

B cell lymphoma proto-oncogene protein

ChAT:

Choline acetyltransferase

Cox:

Cyclooxygenase

DA:

Dopamine

GABA:

γ-Aminobutyric acid

GPR50:

G-protein receptor 50 ortholog

GPx:

Glutathione peroxidase

GRd:

Glutathione reductase

GSH:

Reduced glutathione

GSK–3:

Glycogen synthase kinase-3

iNOS:

Inducible nitric oxide synthase

l-DOPA:

l-Dihydroxyphenylalanine

MAO:

Monoamine oxidase

MAP:

Microtubule-associated protein

MCI:

Mild cognitive impairment

MPP+ :

1-Methyl-4-phenylpyridinium

MPTP:

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

mPTP:

Mitochondrial permeability transition pore

mRNA:

Messenger ribonucleic acid

MT1 :

Melatonin receptor 1

MT2 :

Melatonin receptor 2

MT3 :

Melatonin receptor 3

NF κB:

Nuclear factor κB

nNOS:

Neuronal nitric oxide synthase

NO:

Nitric oxide

PD:

Parkinson’s disease

PK:

Protein kinase

RBD:

REM-associated sleep behavior disorder

REM:

Rapid eye movement

RNS:

Reactive nitrogen species

ROR:

Retinoic acid receptor-related orphan receptor

ROS:

Reactive oxygen species

RZR:

Retinoid Z receptor

SCN:

Suprachiasmatic nuclei

SNpc:

Substantia nigra pars compacta

SOD:

Superoxide dismutase

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Acknowledgments

Studies in authors’ laboratories were supported by grants from the Agencia Nacional de Promoción Científica y Tecnológica, Argentina (PICT 2012 0984), and the University of Buenos Aires. DPC is a Research Career Awardee from the Argentine Research Council (CONICET) and Professor Emeritus, University of Buenos Aires. DEV and LIB are Research Career Awardees from CONICET.

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None is declared.

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Authors and Affiliations

  1. Departamento de Docencia e Investigación, Facultad de Ciencias Médicas, Pontificia Universidad Católica Argentina, Av. Alicia Moreau de Justo 1500, 4 piso, 1107, Buenos Aires, Argentina

    Daniel P. Cardinali M.D., Ph.D., Daniel E. Vigo M.D., Ph.D. & María F. Vidal M.D.

  2. Centro de Neuropsiquiatría y Neurología de la Conducta, Hospital de Clínicas “José de San Martín”, Facultad de Medicina, Universidad de Buenos Aires, Buenos Aires, Argentina

    Natividad Olivar M.D. & Luis I. Brusco M.D., Ph.D.

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  1. Daniel P. Cardinali M.D., Ph.D.
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  2. Daniel E. Vigo M.D., Ph.D.
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  3. Natividad Olivar M.D.
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  4. María F. Vidal M.D.
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  5. Luis I. Brusco M.D., Ph.D.
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Correspondence to Daniel P. Cardinali M.D., Ph.D. .

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Editors and Affiliations

  1. Faculty of Medicine, Department of General Surgery, Gazi University, Besevler, Ankara, Turkey

    Atilla Engin

  2. Faculty of Pharmacy, Department of Toxicology, Gazi University, Hipodrom, Ankara, Turkey

    Ayse Basak Engin

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Cardinali, D.P., Vigo, D.E., Olivar, N., Vidal, M.F., Brusco, L.I. (2015). Therapeutical Implications of Melatonin in Alzheimer’s and Parkinson’s Diseases. In: Engin, A., Engin, A. (eds) Tryptophan Metabolism: Implications for Biological Processes, Health and Disease. Molecular and Integrative Toxicology. Humana Press, Cham. https://doi.org/10.1007/978-3-319-15630-9_9

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