TY - JOUR
T1 - Role of melatonin in Alzheimer's disease
T2 - From preclinical studies to novel melatonin-based therapies
AU - Roy, Jaydeep
AU - Wong, Kan Yin
AU - Aquili, Luca
AU - Uddin, Md Sahab
AU - Heng, Boon Chin
AU - Tipoe, George Lim
AU - Wong, Kah Hui
AU - Fung, Man Lung
AU - Lim, Lee Wei
N1 - Publisher Copyright:
© 2022 Elsevier Inc.
PY - 2022/4
Y1 - 2022/4
N2 - Melatonin and novel melatonin-based therapies such as melatonin-containing hybrid molecules, melatonin analogues, and melatonin derivatives have been investigated as potential therapeutics against Alzheimer's disease (AD) pathogenesis. In this review, we examine the developmental trends of melatonin therapies for AD from 1997 to 2021. We then highlight the neuroprotective mechanisms of melatonin therapy derived from preclinical studies. These mechanisms include the alleviation of amyloid-related burden, neurofibrillary tangle accumulation, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, and impaired neuroplasticity and neurotransmission. We further illustrate the beneficial effects of melatonin on behavior in animal models of AD. Next, we discuss the clinical effects of melatonin on sleep, cognition, behavior, psychiatric symptoms, electroencephalography findings, and molecular biomarkers in patients with mild cognitive impairment and AD. We then explore the effectiveness of novel melatonin-based therapies. Lastly, we discuss the limitations of current melatonin therapies for AD and suggest two emerging research themes for future study.
AB - Melatonin and novel melatonin-based therapies such as melatonin-containing hybrid molecules, melatonin analogues, and melatonin derivatives have been investigated as potential therapeutics against Alzheimer's disease (AD) pathogenesis. In this review, we examine the developmental trends of melatonin therapies for AD from 1997 to 2021. We then highlight the neuroprotective mechanisms of melatonin therapy derived from preclinical studies. These mechanisms include the alleviation of amyloid-related burden, neurofibrillary tangle accumulation, oxidative stress, neuroinflammation, apoptosis, mitochondrial dysfunction, and impaired neuroplasticity and neurotransmission. We further illustrate the beneficial effects of melatonin on behavior in animal models of AD. Next, we discuss the clinical effects of melatonin on sleep, cognition, behavior, psychiatric symptoms, electroencephalography findings, and molecular biomarkers in patients with mild cognitive impairment and AD. We then explore the effectiveness of novel melatonin-based therapies. Lastly, we discuss the limitations of current melatonin therapies for AD and suggest two emerging research themes for future study.
KW - Alzheimer's disease
KW - Melatonin
KW - Mild cognitive impairment
KW - Neuroprotection
KW - Novel melatonin-based therapies
UR - http://www.scopus.com/inward/record.url?scp=85124649561&partnerID=8YFLogxK
U2 - 10.1016/j.yfrne.2022.100986
DO - 10.1016/j.yfrne.2022.100986
M3 - Review article
C2 - 35167824
AN - SCOPUS:85124649561
SN - 0091-3022
VL - 65
JO - Frontiers in Neuroendocrinology
JF - Frontiers in Neuroendocrinology
M1 - 100986
ER -