Alzheimer’s Disease: Focus on the Neuroprotective Role of Melatonin

Abstract

Alzheimer's disease (AD) is characterized by a progressive loss of memory and cognitive function, and by behavioural and sleep disturbances, including insomnia. The pathophysiology of AD has been attributed to oxidative stress-induced amyloid-β protein (Aβ) deposition. Abnormal tau protein, mitochondrial dysfunction and protein hyper-phosphorylation have been demonstrated in neural tissues of AD patients. AD patients exhibit severe sleep-wake disturbances and these sleep disturbances are associated with rapid cognitive decline and memory impairment. Optimally effective management of AD patients will likely require a drug that can arrest Aβ -induced neurotoxic effects and can also restore the disturbed sleep-wake rhythm, with improvement in sleep quality. In this context, the pineal hormone melatonin has been demonstrated to be an effective antioxidant that can prevent Aβ -induced neurotoxic effects through a variety of mechanisms. Sleep deprivation itself produces many effects including oxidative damage, impaired mitochondrial function, neurodegenerative inflammation, altered proteosomal processing and abnormal activation of enzymes. In addition to treating the signs and symptoms of AD, treatment of sleep disturbances may also be necessary for preventing and arresting AD progression. Besides melatonin, a number of melatonergic agonists such as ramelteon, agomelatine and tasimelteon are now used clinically for treating insomnia and other sleep disorders. Their use may also be beneficial in treating Alzheimer's disease.

Systemic Transplantation of Human Umbilical Cord Derived Mesenchymal Stem Cells-Educated T Regulatory Cells Improved the Impaired Cognition in AβPPswe/PS1dE9 Transgenic Mice

“…It has been estimated that about 35.6 million people lived with dementia in 2010, with 4.6 million new cases arising every year [4,5]. The etiology of Alzheimer’s disease, whose neuropathology is characterized by the deposition of extracellular amyloid beta protein (Aβ) and neurofibrillary tangle formation within neurons, remains unclear [6]. It has been hypothesized that the imbalance of the production and degradation of Aβ protein is considered to be the principal initiating factor.…”