Melatonin in Alzheimer’s Disease: A Latent Endogenous Regulator of Neurogenesis to Mitigate Alzheimer’s Neuropathology

Md Farhad Hossain, Md Sahab Uddin*, G. M.Sala Uddin, Dewan Md Sumsuzzman, Md Siddiqul Islam, George E. Barreto, Bijo Mathew, Ghulam Md Ashraf

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review

111 Citations (Scopus)

Abstract

Melatonin, a pineal gland synthesized neurohormone is known as a multifunctioning pleiotropic agent which has a wide range of neuroprotective role in manifold age-related neurodegenerative disorders especially Alzheimer’s diseases (AD). AD is a devastating neurodegenerative disorder and common form of dementia which is defined by abnormal and excessive accumulation of several toxic peptides including amyloid β (Aβ) plaques and neurofibrillary tangles (NFTs). The Alzheimer’s dementia relates to atrophic changes in the brain resulting in loss of memory, cognitive dysfunction, and impairments of the synapses. Aging, circadian disruption, Aβ accumulation, and tau hyperphosphorylation are the utmost risk factor regarding AD pathology. To date, there is no exact treatment against AD progression. In this regard, melatonin plays a crucial role for the inhibition of circadian disruption by controlling clock genes and also attenuates Aβ accumulation and tau hyperphosphorylation by regulating glycogen synthase kinase-3 (GSK3) and cyclin-dependent kinase-5 (CDK5) signaling pathway. In this review, we highlight the possible mechanism of AD etiology and how melatonin influences neurogenesis by attenuating circadian disruption, Aβ formation, as well as tau hyperphosphorylation. Furthermore, we also find out and summarize the neuroprotective roles of melatonin by the blockage of Aβ production, Aβ oligomerization and fibrillation, tau hyperphosphorylation, synaptic dysfunction, oxidative stress, and neuronal death during AD progression.

Original languageEnglish
Pages (from-to)8255-8276
Number of pages22
JournalMolecular Neurobiology
Volume56
Issue number12
DOIs
Publication statusPublished - 1 Dec 2019
Externally publishedYes

Keywords

  • Alzheimer’s disease
  • Amyloid β
  • Circadian rhythm
  • Melatonin
  • Neurofibrillary tangles

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