Melatonin: Clinical Perspectives in Neurodegeneration

Cardinali, Daniel P.

doi:10.3389/fendo.2019.00480

Cited by 156 publications

(147 citation statements)

References 244 publications

(187 reference statements)

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“…*P < 0.05; **P < 0.01; ***P < 0.001. degenerative models (34,(60)(61)(62). Melatonin, at the pharmacologic dose used to exert antiinflammatory effects, likely saturates the melatonin receptor (63). Thus the melatonin effects likely include both receptor-mediated and non-receptor-mediated melatonin effects, including protecting mitochondria by scavenging ROS, inhibiting the mitochondrial permeability transition pore, and activating uncoupling proteins, which maintains the optimal mitochondrial membrane potential (37).…”

Section: Discussionmentioning

confidence: 99%

Melatonin inhibits cytosolic mitochondrial DNA–induced neuroinflammatory signaling in accelerated aging and neurodegeneration

Jauhari¹,

Баранов²,

Suofu³

et al. 2020

Journal of Clinical Investigation

130

104

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Section: Discussionmentioning

confidence: 99%

Melatonin inhibits cytosolic mitochondrial DNA–induced neuroinflammatory signaling in accelerated aging and neurodegeneration

Jauhari¹,

Баранов²,

Suofu³

et al. 2020

Journal of Clinical Investigation

130

104

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“…In agreement, animal studies have shown melatonin to be an effective neuroprotectant in a number of neurodegenerative conditions such as hypoxia/ischemia [5][6][7], Alzheimer's Disease [8], Parkinson's Disease [9], and spinal cord injury [10]. Notably, clinical trials have been designed to establish the potential neuroprotective efficacy of melatonin in humans [11].…”

Section: Introductionmentioning

confidence: 87%

SIRT1 Mediates Melatonin’s Effects on Microglial Activation in Hypoxia: In Vitro and In Vivo Evidence

et al. 2020

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Melatonin exerts direct neuroprotection against cerebral hypoxic damage, but the mechanisms of its action on microglia have been less characterized. Using both in vitro and in vivo models of hypoxia, we here focused on the role played by silent mating type information regulation 2 homolog 1 (SIRT1) in melatonin’s effects on microglia. Viability of rat primary microglia or microglial BV2 cells and SH-SY5Y neurons was significantly reduced after chemical hypoxia with CoCl2 (250 μM for 24 h). Melatonin (1 μM) significantly attenuated CoCl2 toxicity on microglia, an effect prevented by selective SIRT1 inhibitor EX527 (5 μM) and AMP-activated protein kinase (AMPK) inhibitor BML-275 (2 μM). CoCl2 did not modify SIRT1 expression, but prevented nuclear localization, while melatonin appeared to restore it. CoCl2 induced nuclear localization of hypoxia-inducible factor-1α (HIF-1α) and nuclear factor-kappa B (NF-kB), an effect contrasted by melatonin in an EX527-dependent fashion. Treatment of microglia with melatonin attenuated potentiation of neurotoxicity. Common carotid occlusion was performed in p7 rats, followed by intraperitoneal injection of melatonin (10 mg/kg). After 24 h, the number of Iba1+ microglia in the hippocampus of hypoxic rats was significantly increased, an effect not prevented by melatonin. At this time, SIRT1 was only detectable in the amoeboid, Iba1+ microglial population selectively localized in the corpus callosum. In these cells, nuclear localization of SIRT1 was significantly lower in hypoxic animals, an effect prevented by melatonin. NF-kB showed an opposite expression pattern, where nuclear localization in Iba1+ cells was significantly higher in hypoxic, but not in melatonin-treated animals. Our findings provide new evidence for a direct effect of melatonin on hypoxic microglia through SIRT1, which appears as a potential pharmacological target against hypoxic-derived neuronal damage.

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“…These rhythms are involved in aging, carcinogenesis, and a number of diseases [4,[10][11][12][13][14][15][16]. Clinical research is underway in various fields including the application of melatonin in treating biological rhythm abnormalities, glucose and lipid metabolism disorders, immunoregulation, anticancer effects and aging-related diseases (Parkinson's and Alzheimer's disease) [17][18][19][20][21].…”

Section: Introductionmentioning

confidence: 99%

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

Tamura

Jozaki

Tanabe

et al. 2020

IJMS

162

105

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Melatonin is probably produced in all cells but is only secreted by the pineal gland. The pineal secretion of melatonin is determined by the light-dark cycle, and it is only released at night. Melatonin regulates biological rhythms via its receptors located in the suprachiasmatic nuclei of the hypothalamus. Melatonin also has strong antioxidant activities to scavenge free radicals such as reactive oxygen species (ROS). The direct free radical scavenging actions are receptor independent. ROS play an important role in reproductive function including in the ovulatory process. However, excessive ROS can also have an adverse effect on oocytes because of oxidative stress, thereby causing infertility. It is becoming clear that melatonin is located in the ovarian follicular fluid and in the oocytes themselves, which protects these cells from oxidative damage as well as having other beneficial actions in oocyte maturation, fertilization, and embryo development. Trials on humans have investigated the improvement of outcomes of assisted reproductive technology (ART), such as in vitro fertilization and embryo transfer (IVF-ET), by way of administering melatonin to patients suffering from infertility. In addition, clinical research has examined melatonin as an anti-aging molecule via its antioxidative actions, and its relationship with the aging diseases, e.g., Alzheimer's and Parkinson's disease, is also underway. Melatonin may also reduce ovarian aging, which is a major issue in assisted reproductive technology. This review explains the relationship between melatonin and human reproductive function, as well as the clinical applications expected to improve the outcomes of assisted reproductive technology such as IVF, while also discussing possibilities for melatonin in preventing ovarian aging.

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Melatonin: Clinical Perspectives in Neurodegeneration

Cited by 156 publications

References 244 publications

Melatonin inhibits cytosolic mitochondrial DNA–induced neuroinflammatory signaling in accelerated aging and neurodegeneration

Melatonin inhibits cytosolic mitochondrial DNA–induced neuroinflammatory signaling in accelerated aging and neurodegeneration

SIRT1 Mediates Melatonin’s Effects on Microglial Activation in Hypoxia: In Vitro and In Vivo Evidence

Importance of Melatonin in Assisted Reproductive Technology and Ovarian Aging

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