Role of melatonin in Alzheimer-like neurodegeneration
Abstract
Alzheimer disease (AD), an age-related neurodegenerative disorder with progressive
loss of memory and deterioration of comprehensive cognition, is characterized
by extracellular senile plaques of aggregated β-amyloid (Aβ), and intracellular
neurofibrillary tangles that contain hyperphosphorylated tau protein. Recent
studies showed that melatonin, an indoleamine secreted by the pineal gland, may
play an important role in aging and AD as an antioxidant and neuroprotector.
Melatonin decreases during aging and patients with AD have a more profound
reduction in this hormone. Data from clinical trials indicate that melatonin supplementation
improves sleep, ameliorates sundowning, and slows down the progression
of cognitive impairment in Alzheimer’s patients. Melatonin efficiently protects
neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid
properties: it not only inhibits Aβ generation, but also arrests the formation of
amyloid fibrils by a structure-dependent interaction with Aβ. Our recent studies
have demonstrated that melatonin efficiently attenuates Alzheimer-like tau
hyperphosphorylation. Although the exact mechanism is still not fully understood,
a direct regulatory influence of melatonin on the activities of protein kinases and
protein phosphatases is proposed. Additionally, melatonin also plays a role in
protecting cholinergic neurons and in anti-inflammation. Here, the neuroprotective
effects of melatonin and the underlying mechanisms by which it exerts its effects
are reviewed. The capacity of melatonin to prevent or ameliorate tau and Aβ
pathology further enhances its potential in the prevention or treatment of AD.
Keywords:
loss of memory and deterioration of comprehensive cognition, is characterized
by extracellular senile plaques of aggregated β-amyloid (Aβ), and intracellular
neurofibrillary tangles that contain hyperphosphorylated tau protein. Recent
studies showed that melatonin, an indoleamine secreted by the pineal gland, may
play an important role in aging and AD as an antioxidant and neuroprotector.
Melatonin decreases during aging and patients with AD have a more profound
reduction in this hormone. Data from clinical trials indicate that melatonin supplementation
improves sleep, ameliorates sundowning, and slows down the progression
of cognitive impairment in Alzheimer’s patients. Melatonin efficiently protects
neuronal cells from Aβ-mediated toxicity via antioxidant and anti-amyloid
properties: it not only inhibits Aβ generation, but also arrests the formation of
amyloid fibrils by a structure-dependent interaction with Aβ. Our recent studies
have demonstrated that melatonin efficiently attenuates Alzheimer-like tau
hyperphosphorylation. Although the exact mechanism is still not fully understood,
a direct regulatory influence of melatonin on the activities of protein kinases and
protein phosphatases is proposed. Additionally, melatonin also plays a role in
protecting cholinergic neurons and in anti-inflammation. Here, the neuroprotective
effects of melatonin and the underlying mechanisms by which it exerts its effects
are reviewed. The capacity of melatonin to prevent or ameliorate tau and Aβ
pathology further enhances its potential in the prevention or treatment of AD.