Alzheimer’s disease: pathological mechanisms and the beneficial role of melatonin

Abstract

: Alzheimer’s disease (AD) is a highly complex neurodegenerative disorder of the aged that has multiple factors which contribute to its etiology in terms of initiation and progression. This review summarizes these diverse aspects of this form of dementia. Several hypotheses, often with overlapping features, have been formulated to explain this debilitating condition. Perhaps the best‐known hypothesis to explain AD is that which involves the role of the accumulation of amyloid‐β peptide in the brain. Other theories that have been invoked to explain AD and summarized in this review include the cholinergic hypothesis, the role of neuroinflammation, the calcium hypothesis, the insulin resistance hypothesis, and the association of AD with peroxidation of brain lipids. In addition to summarizing each of the theories that have been used to explain the structural neural changes and the pathophysiology of AD, the potential role of melatonin in influencing each of the theoretical processes involved is discussed. Melatonin is an endogenously produced and multifunctioning molecule that could theoretically intervene at any of a number of sites to abate the changes associated with the development of AD. Production of this indoleamine diminishes with increasing age, coincident with the onset of AD. In addition to its potent antioxidant and anti‐inflammatory activities, melatonin has a multitude of other functions that could assist in explaining each of the hypotheses summarized above. The intent of this review is to stimulate interest in melatonin as a potentially useful agent in attenuating and/or delaying AD.

La melatonina como un factor promotor de la diferenciación neuronal: implicaciones en el tratamiento de las demencias

“…63 La administración de esta indolamina a sujetos que padecen EA causa una mejoría en los trastornos de los ritmos circadianos [64][65][66] así como una reducción en la disfunción cognitiva. 67 Los estudios preclínicos apoyan este concepto ya que la MEL actúa como un captador de radicales libres y por lo tanto reduce el estrés oxidativo y la apoptosis.…”

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

“…In addition to inhibiting mitochondrial respiratory complex activities in AD patients, disturbances in mitochondrial dynamics have also been demonstrated. This includes disturbances in mitochondrial structure, impairment of dynamin -related peptide (Drp1) and imbalances in fission and fusion, with consequent neuronal damage and synaptic loss [27]. Significant disturbances of mitochondrial proteins and lipids also occur following intramitochondrial accumulation of Aβ, which in turn causes functional impairment of mitochondria in AD [26].…”

Constructing and characterizing a bioactive small molecule and microRNA association network for Alzheimer's disease

“…learning and memory) impairment [61] and is associated with Ab [62]. Rosales-Corral et al [63] suggested that melatonin could present multiple potential functions that correspond to several possible pathological mechanisms including the cholinergic hypothesis. Moreover, 'melatoninergic' or melatonin-type drugs may relieve dementia-related cognitive deficits and other syndromes [64,65].…”