Evidence of Oxidative Stress in Alzheimer's Disease Brain and Antioxidant Therapy

Annals of the New York Academy of Sciences, Год журнала: 2008, Номер 1147(1), С. 70 - 78

Опубликована: Дек. 1, 2008

Alzheimer's disease (AD) is the most common form of neurodegenerative associated with dementia in elderly. Although initiating events are still unknown, it clear that AD, at least its sporadic form, results from combination genetic risk factors different epigenetic events. Among them, a growing body evidence suggests an imbalance between free radical formation and destruction involved AD pathogenesis. This concept originally derived hypothesis aging, which states age‐related accumulation radicals damaged cell components. The fact age key factor provides support for this hypothesis. There long list surrogate markers, includes lipid, DNA, protein oxidation, oxidant stress‐mediated injury have been reported as elevated brain. Moreover, epidemiologic studies show dietary intake natural or synthetic products putative antioxidant effect, such (but not only) vitamin E, reduces AD. On other hand, antioxidative intervention animal models AD‐like amyloidosis significant reduction amyloid β deposition behavioral improvements. However, randomized clinical trial E supplementation patients shows only marginal positive effect. Another study reports no effect on rate progression subjects mild cognitive impairment. article will review both promises caveats available data propose future directions to be taken addressing them.

Язык: Английский

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Aging, Melatonin, and the Pro- and Anti-Inflammatory Networks

International Journal of Molecular Sciences, Год журнала: 2019, Номер 20(5), С. 1223 - 1223

Опубликована: Март 11, 2019

Aging and various age-related diseases are associated with reductions in melatonin secretion, proinflammatory changes the immune system, a deteriorating circadian sirtuin-1 (SIRT1) activity. In non-tumor cells, several effects of abolished by inhibiting SIRT1, indicating mediation SIRT1. Melatonin is, addition to its antioxidant roles, an stimulatory agent. However, it can act as either pro- or anti-inflammatory regulator context-dependent way. stimulate release cytokines other mediators, but also, under different conditions, suppress inflammation-promoting processes such NO release, activation cyclooxygenase-2, inflammasome NLRP3, gasdermin D, toll-like receptor-4 mTOR signaling, cytokine SASP (senescence-associated secretory phenotype), amyloid-β toxicity. It also activates network, which SIRT1 activation, upregulation Nrf2 downregulation NF-κB, IL-4 IL-10 involved. A perhaps crucial action may be promotion macrophage microglia polarization favor phenotype M2. addition, many factors networks subject regulation microRNAs that target mRNAs respective upregulate them targeting their inhibitor proteins.

Язык: Английский

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

Journal of Pineal Research, Год журнала: 2011, Номер 52(2), С. 167 - 202

Опубликована: Окт. 10, 2011

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

Язык: Английский

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Biological metals and Alzheimer's disease: Implications for therapeutics and diagnostics

Progress in Neurobiology, Год журнала: 2010, Номер 92(1), С. 1 - 18

Опубликована: Май 3, 2010

Язык: Английский

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Monoaminergic neuropathology in Alzheimer’s disease

Progress in Neurobiology, Год журнала: 2016, Номер 151, С. 101 - 138

Опубликована: Апрель 12, 2016

Язык: Английский

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