Therapeutic potential of neurogenesis and melatonin regulation in Alzheimer's disease

• Published in: Annals of the New York Academy of Sciences Vol. 1478; no. 1; pp. 43 - 62
• Main Authors: Mihardja, Mazel, Roy, Jaydeep, Wong, Kan Yin, Aquili, Luca, Heng, Boon Chin, Chan, Ying‐Shing, Fung, Man Lung, Lim, Lee Wei
• Format: Journal Article
• Language: English
• Published: United States Wiley Subscription Services, Inc 01-10-2020
• Subjects: Alzheimer Disease - metabolism; Alzheimer Disease - pathology; Alzheimer Disease - therapy; Alzheimer's disease; Amyloid beta-Peptides - genetics; Animals; Brain - metabolism; Brain - pathology; Cell differentiation; Cell survival; Circadian Rhythm - drug effects; Circadian Rhythm - genetics; Circadian rhythms; Cognitive ability; Cognitive Dysfunction - pathology; Cognitive Dysfunction - therapy; Disease Models, Animal; Humans; Impairment; Melatonin; Melatonin - genetics; Melatonin - therapeutic use; Neurodegenerative diseases; Neurofibrillary tangles; Neurogenesis; Neurogenesis - genetics; Neurons - drug effects; Neurons - pathology; Pineal gland; Plaques; preclinical; Signs and symptoms; neurogenesis; melatonin; preclinical; Alzheimer's disease
• ISSN: 0077-8923; 1749-6632
• DOI: 10.1111/nyas.14436

Alzheimer's disease (AD) is an age‐related neurodegenerative disorder characterized by the hallmark pathologies of amyloid‐beta plaques and neurofibrillary tangles. Symptoms of this devastating disease include behavioral changes and deterioration of higher cognitive functions. Impairment of neurogenesis has also been shown to occur in AD, which adversely impacts new neuronal cell growth, differentiation, and survival. This impairment possibly results from the cumulative effects of the various pathologies of AD. Preclinical studies have suggested that the administration of melatonin—the pineal hormone primarily responsible for the regulation of the circadian rhythm—targets the effects of AD pathologies and improves cognitive impairment. It is postulated that by mitigating the effect of these pathologies, melatonin can also rescue neurogenesis impairment. This review aims to explore the effect of AD pathologies on neurogenesis, as well as the mechanisms by which melatonin is able to ameliorate AD pathologies to potentially promote neurogenesis.
Melatonin downregulation and neurogenesis impairment are linked to AD. Our review briefly discusses the different pathways in which neurogenesis is affected in AD. We summarize the protective effects of melatonin in relation to neurodegeneration in AD and the proposed neuroprotective mechanisms, and then discuss the current state of preclinical melatonin treatments. Overall, this review may provide some clarity on the potential effects of melatonin regulation on neurogenesis in AD.