Role of melatonin in Alzheimer’s disease: From preclinical studies to novel melatonin-based therapies

Roy, Jaydeep; Wong, Kan Yin; Aquili, Luca; Uddin, Md. Sahab; Heng, Boon Chin; Tipoe, George L.; Fung, Man Lung; Lim, Lee Wei

doi:10.1016/j.yfrne.2022.100986

Cited by 26 publications

(19 citation statements)

References 174 publications

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“…These and other studies have also revealed the primary binding regions for these phytochemicals providing an introductory roadmap on how to find and develop new and more effective phytochemical-based drugs to stop Aβ aggregation. While it was beyond the scope of this review, a number of recent reviews have focused on research on the phytochemicals covered here outlining the type of study, organisms used and the resulting AD pathophysiological benefits [ 32 , 89 , 90 , 91 , 92 , 93 , 94 ].…”

Section: Discussionmentioning

confidence: 99%

“…Melatonin, quercetin and curcumin, three phytochemicals widely touted for their value in the treatment of AD, all bind to CaM [ 28 , 29 , 30 ]. A product of the pineal gland, melatonin (N-acetyl-5-methoxytryptamine) is a multifunctional hormone that regulates blood pressure, body temperature, circadian rhythm and sleep [ 31 , 32 ]. Melatonin has antioxidant, immunomodulatory and other activities that play a role in neurodegenerative diseases, such as Alzheimer’s.…”

Section: Calmodulin As a Phytochemical Targetmentioning

confidence: 99%

“…Recent research has revealed that at least part of these diverse and central functions is due to melatonin binding to CaM and its effects on BACE1 and other AD-related calmodulin-binding proteins. The preclinical and clinical research on melatonin that was carried out up to 2021 was reviewed but despite the detail, the melatonin’s impact on calcium and calmodulin signal transduction was overlooked [ 32 ].…”

Section: Calmodulin As a Phytochemical Targetmentioning

confidence: 99%

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Phytochemical Interactions with Calmodulin and Critical Calmodulin Binding Proteins Involved in Amyloidogenesis in Alzheimer’s Disease

O’Day

2023

Biomolecules

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An increasing number of plant-based herbal treatments, dietary supplements, medical foods and nutraceuticals and their component phytochemicals are used as alternative treatments to prevent or slow the onset and progression of Alzheimer’s disease. Their appeal stems from the fact that no current pharmaceutical or medical treatment can accomplish this. While a handful of pharmaceuticals are approved to treat Alzheimer’s, none has been shown to prevent, significantly slow or stop the disease. As a result, many see the appeal of alternative plant-based treatments as an option. Here, we show that many phytochemicals proposed or used as Alzheimer’s treatments share a common theme: they work via a calmodulin-mediated mode of action. Some phytochemicals bind to and inhibit calmodulin directly while others bind to and regulate calmodulin-binding proteins, including Aβ monomers and BACE1. Phytochemical binding to Aβ monomers can prevent the formation of Aβ oligomers. A limited number of phytochemicals are also known to stimulate calmodulin gene expression. The significance of these interactions to amyloidogenesis in Alzheimer’s disease is reviewed.

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Section: Discussionmentioning

confidence: 99%

Section: Calmodulin As a Phytochemical Targetmentioning

confidence: 99%

Section: Calmodulin As a Phytochemical Targetmentioning

confidence: 99%

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Phytochemical Interactions with Calmodulin and Critical Calmodulin Binding Proteins Involved in Amyloidogenesis in Alzheimer’s Disease

O’Day

2023

Biomolecules

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“…Another animal model study performed in mice investigated novel drug-based therapies that could be used to reduce the onset of status epilepticus (SE), and the authors hypothesized that melatonin is a therapeutic target for neurodegenerative diseases such as AD, Parkinson’s disease, and epilepsy. To test their hypothesis, the authors used ICR mice, inducting to SE with kainate (KA); after a series of tests, the authors identified a compound indole derivate 3e containing 2-furyl fragment, which is effective against KA-induced SE and oxidative effects and is similar to melatonin [ 51 ]. The extent of the therapeutic potential of melatonin is still unclear, but part of the melatonin neuroprotective effect has been explained by the presence of melatonin receptors in special melatonin receptor 1 in the injured cells [ 52 ].…”

Section: In Vivo Animal Model For the Study Of Pineal Glandmentioning

confidence: 99%

Pineal Gland from the Cell Culture to Animal Models: A Review

Peruri

Morgan

D’Souza

et al. 2022

Life

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This review demonstrates current literature on pineal gland physiology, pathology, and animal model experiments to concisely explore future needs in research development with respect to pineal gland function and neuro-regenerative properties. The pineal gland plays an integral role in sleep and recovery by promoting physiologic circadian rhythms via production and release of melatonin. Yet, the current literature shows that the pineal gland has neuroprotective effects that modulate both peripheral and central nerve injuries through several direct and indirect mechanisms, such as angiogenesis and induction of growth factors and anti-inflammatory mediators. Animal models have also shown correlations between pineal gland function and metabolic homeostasis. Studies have shown that a functional pineal gland is essential in preventing and slowing the progression of certain diseases such as diabetes, osteoporosis, vertebral osteoarthritis, and neurodegenerative processes. Lastly, the array of cell culturing methods and animal models that can be used to further develop the study of pineal gland function and nervous system injury were reviewed.

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“…It participates in regulating the immune, reproductive, endocrine and central nervous systems, and has attracted widespread attention due to its strong anti-inflammatory and antioxidant properties (Majidinia et al, 2018;He et al, 2021;Kvetnoy et al, 2022). Recent studies have shown that melatonin exerts a neuroprotective role in many neurological diseases such as stroke (Lee et al, 2007;Tai et al, 2010), trauma injury (Samantaray et al, 2009;Osier et al, 2018), neurodegenerative diseases (Alamdari et al, 2021;Roy et al, 2022), and spinal cord injury (Hong et al, 2010;Zhang et al, 2018). The mechanisms involved include anti-inflammation, anti-apoptosis, anti-oxidative stress, and BBB protection.…”

Section: Introductionmentioning

confidence: 99%

Melatonin as a Potential Neuroprotectant: Mechanisms in Subarachnoid Hemorrhage-Induced Early Brain Injury

2022

Front. Aging Neurosci.

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Subarachnoid hemorrhage (SAH) is a common cerebrovascular disease with high mortality and disability rates. Despite progressive advances in drugs and surgical techniques, neurological dysfunction in surviving SAH patients have not improved significantly. Traditionally, vasospasm has been considered the main cause of death and disability following SAH, but anti-vasospasm therapy has not benefited clinical prognosis. Many studies have proposed that early brain injury (EBI) may be the primary factor influencing the prognosis of SAH. Melatonin is an indole hormone and is the main hormone secreted by the pineal gland, with low daytime secretion levels and high nighttime secretion levels. Melatonin produces a wide range of biological effects through the neuroimmune endocrine network, and participates in various physiological activities in the central nervous system, reproductive system, immune system, and digestive system. Numerous studies have reported that melatonin has extensive physiological and pharmacological effects such as anti-oxidative stress, anti-inflammation, maintaining circadian rhythm, and regulating cellular and humoral immunity. In recent years, more and more studies have been conducted to explore the molecular mechanism underlying melatonin-induced neuroprotection. The studies suggest beneficial effects in the recovery of intracerebral hemorrhage, cerebral ischemia-reperfusion injury, spinal cord injury, Alzheimer’s disease, Parkinson’s disease and meningitis through anti-inflammatory, antioxidant and anti-apoptotic mechanisms. This review summarizes the recent studies on the application and mechanism of melatonin in SAH.

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Role of melatonin in Alzheimer’s disease: From preclinical studies to novel melatonin-based therapies

Cited by 26 publications

References 174 publications

Phytochemical Interactions with Calmodulin and Critical Calmodulin Binding Proteins Involved in Amyloidogenesis in Alzheimer’s Disease

Phytochemical Interactions with Calmodulin and Critical Calmodulin Binding Proteins Involved in Amyloidogenesis in Alzheimer’s Disease

Pineal Gland from the Cell Culture to Animal Models: A Review

Melatonin as a Potential Neuroprotectant: Mechanisms in Subarachnoid Hemorrhage-Induced Early Brain Injury

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