The DOI matches its Crossref record; 738 of the 738 references it cites were found in a registry or an index.
Melatonin—A pleiotropic, orchestrating regulator molecule
Open accessAbstract
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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“As a cytoprotective molecule, melatonin reverses inflammatory damage, scavenges free radicals, and facilitates the immune response.78”
From From combinations to multitarget-directed ligands: A continuum in Alzheimer’s disease polypharmacology (2021) · cites this paper as [78]
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3 retracted
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Self-citation
Metadata
- 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
- Venue
- Progress in Neurobiology
- Publisher
- Elsevier BV
- Published
- 2011-03
- Volume
- 93
- Issue
- 3
- Pages
- 350-384
- ISSN
- 0301-0082 (ISSN-L)
- 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
- 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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