Cited by 845Circadian rhythm and melatoninmelanin and skin pigmentationImpact of Light on Environment and Health

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Melatonin—A pleiotropic, orchestrating regulator molecule

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Hardeland, Rüdiger, Cardinali, Daniel P., Srinivasan, Venkatramanujam, Spence, D. Warren, Brown, Gregory M., Pandi-Perumal, Seithikurippu R.·2011·Progress in Neurobiology

DOI 10.1016/j.pneurobio.2010.12.004

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Abstract

Melatonin, the neurohormone of the pineal gland, is also produced by various other tissues and cells. It acts via G protein-coupled receptors expressed in various areas of the central nervous system and in peripheral tissues. Parallel signaling mechanisms lead to cell-specific control and recruitment of downstream factors, including various kinases, transcription factors and ion channels. Additional actions via nuclear receptors and other binding sites are likely. By virtue of high receptor density in the circadian pacemaker, melatonin is involved in the phasing of circadian rhythms and sleep promotion. Additionally, it exerts effects on peripheral oscillators, including phase coupling of parallel cellular clocks based on alternate use of core oscillator proteins. Direct central and peripheral actions concern the up- or downregulation of various proteins, among which inducible and neuronal NO synthases seem to be of particular importance for antagonizing inflammation and excitotoxicity. The methoxyindole is also synthesized in several peripheral tissues, so that the total content of tissue melatonin exceeds by far the amounts in the circulation. Emerging fields in melatonin research concern receptor polymorphism in relation to various diseases, the control of sleep, the metabolic syndrome, weight control, diabetes type 2 and insulin resistance, and mitochondrial effects. Control of electron flux, prevention of bottlenecks in the respiratory chain and electron leakage contribute to the avoidance of damage by free radicals and seem to be important in neuroprotection, inflammatory diseases and, presumably, aging. Newly discovered influences on sirtuins and downstream factors indicate that melatonin has a role in mitochondrial biogenesis.

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RETRACTED: Melatonin prevents oxidative stress and changes in antioxidant enzyme expression and activity in the liver of aging rats
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RETRACTED: Changes in the expression of melatonin receptors induced by melatonin treatment in hepatocarcinoma HepG2 cells
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RETRACTED: Melatonin prevents lipopolysaccharide‐induced hyporeactivity in rat
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Authors: Hardeland, R., Cardinali, D. P., Srinivasan, V., Spence, D. W., Brown, G. M., & Pandi-Perumal, S. R.
Affiliations: University of Göttingen (DE)
Pontificia Universidad Católica Argentina (AR)
Karpagam Academy of Higher Education (IN)
Centre for Addiction and Mental Health (CA)
Corresponding author: Hardeland, Rüdiger
ORCID: Hardeland, Rüdiger
Cardinali, Daniel P.
Spence, D. Warren
Brown, Gregory M.
Pandi-Perumal, Seithikurippu R.
Venue: Progress in Neurobiology
Publisher: Elsevier BV
Published: 2011-03
Volume: 93
Issue: 3
Pages: 350-384
ISSN: 0301-0082 (ISSN-L)
DOI: 10.1016/j.pneurobio.2010.12.004
OpenAlex: W2157611470
Cited by: 843
References: 733
Citations by year: 2026: 20 · 2025: 38 · 2024: 34 · 2023: 57 · 2022: 71 · 2021: 64 · 2020: 72 · 2019: 67 · 2018: 74 · 2017: 59 · 2016: 61 · 2015: 53 · 2014: 49 · 2013: 58 · 2012: 45
FWCI: 17.92
Type: journal article
Language: en
Open access: green
repositorio.uca.edu.ar
Licence: cc-by-nc-sa
www.elsevier.com/tdm/userlicense/1.0/ (tdm)
Locations: Progress in Neurobiology (publishedVersion)
PubMed (publishedVersion)
LA Referencia (Red Federada de Repositorios Institucionales de Publicaciones Científicas) (submittedVersion, cc-by-nc-sa)
Americanae (AECID Library) (submittedVersion, cc-by-nc-sa)
GRO (submittedVersion)
Topics: Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Circadian rhythm and melatonin
Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
Physical Sciences › Environmental Science › Global and Planetary Change › Impact of Light on Environment and Health
Keywords: melatonin, pineal gland, G protein-coupled receptors, circadian rhythm, sleep regulation, peripheral oscillators, nitric oxide synthase, inflammation, excitotoxicity, metabolic syndrome, type 2 diabetes, insulin resistance, mitochondrial function, mitochondrial biogenesis, sirtuins, neuroprotection, aging
MeSH terms: Aging, Animals, Binding Sites, Circadian Rhythm, Energy Metabolism, Humans, Immune System, Melatonin, Mitochondria, Pineal Gland, Signal Transduction, Receptors, Melatonin

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Melatonin—A pleiotropic, orchestrating regulator molecule

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