The antifibrillogenic effects of melatonin and its metabolites were observed not only in vitro but also in vivo in transgenic mouse models. In this regard, melatonin and other structurally related indolic compounds, such as indole-3-propionic acid, proved to be more potent than classical antioxidants. Moreover, these compounds remained relatively inefficient in preventing Aβ toxicity and fibrillogenesis. Although some studies demonstrated a reduction in lipid peroxidation, epidemiological data showed only minor or no clear-cut clinical effects of classical antioxidants. Classical radical scavengers like vitamins E and C have been used for the treatment of AD patients with only limited success. However, the simplistic concept that reduces AD lesions to oxidative damage has been shown insufficient to explain the disease. Tangles are associated with hyperphosphorylation of tau, a microtubule-associated protein, and of neurofilament H/M subunits, processes that lead to misfolding and accumulation of altered proteins, along with a disruption of microtubules. The deposition of β-amyloid (Aβ) plaques is thought to destabilize neurons by mechanisms which require further clarification. Many mechanisms have been proposed as predisposing for excessive oxidative damage, including the genetic background (e.g., expression levels and subforms of presenilins and apolipoprotein E), inflammatory processes associated with cytokine release, or neurotoxicity by metal ions. In spite of a large number of studies undertaken, the etiology of AD remains largely unknown, although a participation of oxidative stress in the development of neuropathology seems to be warranted. ĪD is an age-associated neurodegenerative disease that is characterized by a progressive loss of cognitive function, loss of memory, and other neurobehavioral manifestations. Since MCI can represent prodromal AD it needs to be adequately diagnosed and treated. This review focuses on the therapeutic potential of melatonin in AD and in minimal cognitive impairment (MCI), an etiologically heterogeneous syndrome which progresses to AD at an approximate rate of 12 % every year. Īmong these substances, melatonin emerges as unique for several reasons: it is a natural compound synthesized in the pineal gland and other body tissues, it can be released by the pineal gland via the pineal recess into the cerebrospinal fluid (CSF), in much higher concentrations than into the circulation, and its production decreases with age, a fact which has been suggested to a the major predisposing factor in neurodegenerative diseases. Therefore, numerous compounds with antioxidant properties have been suggested for treatment of AD and other neurodegenerative diseases. Many recent reviews on AD present compelling evidence for a decisive participation of severe oxidative stress in the development of neuropathology seen in this disease.
#Cardinal chains level 49 free#
This concept is based on the free radical hypothesis of aging as proposed by Harman more than 50 years ago. Oxidative damage has been suggested as the primary cause of aging and age-associated neurodegenerative diseases like Alzheimer’s disease (AD). clinical and subjective relevance) before melatonin´s use can be advocated.
In the case of AD, larger randomized controlled trials are necessary to yield evidence of effectiveness (i.e. The analysis of published evidence made it possible to postulate melatonin as a useful ad-on therapeutic tool in MCI.
Only clinical studies with empirical treatment data were reviewed.
#Cardinal chains level 49 full#
Full publications were obtained and references were checked for additional material where appropriate. Search terms were “Alzheimer” and “melatonin”. PubMed was searched using Entrez for articles including clinical trials and published up to 15 January 2010. The aim of this manuscript was to assess published evidence of the efficacy of melatonin to treat AD and MCI patients. This is of particularly importance in mild cognitive impairment (MCI), an etiologically heterogeneous syndrome that precedes dementia. The antioxidant, mitochondrial and antiamyloidogenic effects of melatonin indicate its potentiality to interfere with the onset of the disease. Melatonin replacement has been shown effective to treat sundowning and other sleep wake disorders in AD patients. Half of severely ill AD patients develop chronobiological day-night rhythm disturbances like an agitated behavior during the evening hours (so-called “sundowning”). Melatonin secretion decreases in Alzheimer´s disease (AD) and this decrease has been postulated as responsible for the circadian disorganization, decrease in sleep efficiency and impaired cognitive function seen in those patients.
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