Decreasing oxidative stress and neuroinflammation with a multifunctional peptide rescues memory deficits in mice with Alzheimer disease

Zhou, Weiwei; Lü, Shan; Su, Ya-jing; Xue, Ding; Yu, Xiaolin; Wang, Shaowei; Zhang, He; Xu, Peng-xin; Xie, Xin; Liu, Rui‐tian

doi:10.1016/j.freeradbiomed.2014.06.013

Cited by 58 publications

(44 citation statements)

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“…Fourth, increased levels of metal ions are found in the AD brain that can potently generate free radicals and enhance protein and DNA oxidation. Moreover, the presence of heme oxygenase-1 and superoxide dismutase-1 (anti-oxidative enzymes) in senile plaques highlight the possible role of oxidative stress in AD (Chauhan and Chauhan 2006;Butterfield et al 2001;Zhou et al 2014). The fact that aging is a key risk factor for AD and that reactive oxygen species accumulate over time provides additional support for the free radical hypothesis of AD pathogenesis.…”

Section: Anti-oxidative Therapymentioning

confidence: 99%

“…Aside from the two major known neuropathological AD hallmarks, senile plaques and neurofibrillary tangles, a number of pathological abnormalities, including microglial activation and inflammatory processes, are found in AD brains (Nuzzo et al 2014;Zhou et al 2014;Kim et al 2008). Chronic inflammatory reactions are also common symptoms among age-related neurodegenerative disorders.…”

Section: Anti-inflammatory Therapymentioning

confidence: 99%

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Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

Thapa

2015

Advances in Experimental Medicine and Biology

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Flavonoids are naturally occurring phytochemicals found in a variety of fruits and vegetables and offer color, flavor, aroma, nutritional and health benefits. Flavonoids have been found to play a neuroprotective role by inhibiting and/or modifying the self-assembly of the amyloid-β (Aβ) peptide into oligomers and fibrils, which are linked to the pathogenesis of Alzheimer's disease. The neuroprotective efficacy of flavonoids has been found to strongly depend on their structure and functional groups. Flavonoids may exist in monomeric, as well as di-, tri-, tetra- or polymeric form through C-C or C-O-C linkages. It has been shown that flavonoids containing two or more units, e.g., biflavonoids, exert greater biological activity than their respective monoflavonoids. For instance, biflavonoids have the ability to distinctly alter Aβ aggregation and more effectively reduce the toxicity of Aβ oligomers compared to the monoflavonoid moieties. Although the molecular mechanisms remain to be elucidated, flavonoids have been shown to alter the Aβ aggregation pathway to yield non-toxic, unstructured Aβ aggregates, as well as directly exerting a neuroprotective effect to cells. In this chapter, we review biflavonoid-mediated Aβ aggregation and toxicity, and highlight the beneficial roles biflavonoids can potentially play in the prevention and treatment of Alzheimer's disease.

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Section: Anti-oxidative Therapymentioning

confidence: 99%

Section: Anti-inflammatory Therapymentioning

confidence: 99%

Biflavonoids as Potential Small Molecule Therapeutics for Alzheimer’s Disease

Thapa

2015

Advances in Experimental Medicine and Biology

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“…Compelling evidence from in vivo and in vitro studies suggest that chronic neuroinflammation participates to the process of many brain disorders, since it is a long-standing and self-perpetuating inflammatory response that persists long after an initial injury or insult in brain (Fuster-Matanzo et al 2013;Zhou et al 2014). Emerging research studies note that neuroinflammation is a causable factor for the pathogenesis of AD, underlying enhancing the production of Ab (the formation of amyloid plaques) and the aberrant hyperphosphorylation of tau (the formation of NFTs) (Verri et al 2012;Faden and Loane 2014;Zhou et al 2014).…”

Section: Rage Signaling Contributes To Ad Pathogenesis Via Activatingmentioning

confidence: 99%

“…Emerging research studies note that neuroinflammation is a causable factor for the pathogenesis of AD, underlying enhancing the production of Ab (the formation of amyloid plaques) and the aberrant hyperphosphorylation of tau (the formation of NFTs) (Verri et al 2012;Faden and Loane 2014;Zhou et al 2014).…”

Section: Rage Signaling Contributes To Ad Pathogenesis Via Activatingmentioning

confidence: 99%

Role of RAGE in Alzheimer’s Disease

et al. 2015

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Receptor for advanced glycation end products (RAGE) is a receptor of the immunoglobulin super family that plays various important roles under physiological and pathological conditions. Compelling evidence suggests that RAGE acts as both an inflammatory intermediary and a critical inducer of oxidative stress, underlying RAGE-induced Alzheimer-like pathophysiological changes that drive the process of Alzheimer's disease (AD). A critical role of RAGE in AD includes beta-amyloid (Aβ) production and accumulation, the formation of neurofibrillary tangles, failure of synaptic transmission, and neuronal degeneration. The steady-state level of Aβ depends on the balance between production and clearance. RAGE plays an important role in the Aβ clearance. RAGE acts as an important transporter via regulating influx of circulating Aβ into brain, whereas the efflux of brain-derived Aβ into the circulation via BBB is implemented by LRP1. RAGE could be an important contributor to Aβ generation via enhancing the activity of β- and/or γ-secretases and activating inflammatory response and oxidative stress. However, sRAGE-Aβ interactions could inhibit Aβ neurotoxicity and promote Aβ clearance from brain. Meanwhile, RAGE could be a promoting factor for the synaptic dysfunction and neuronal circuit dysfunction which are both the material structure of cognition, and the physiological and pathological basis of cognition. In addition, RAGE could be a trigger for the pathogenesis of Aβ and tau hyper-phosphorylation which both participate in the process of cognitive impairment. Preclinical and clinical studies have supported that RAGE inhibitors could be useful in the treatment of AD. Thus, an effective measure to inhibit RAGE may be a novel drug target in AD.

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“…Among these, a particular role is played by glutathione (GSH, L-γ-glutamyl-L-cysteinylglycine), is endogenous peptide present in all mammalian cells in considerable concentrations and functioning as regulator [7,11]. Disturbance of the thiol-disulfide balance, i.e., of the ratio of the oxidized (disulfide, -S-S-) and reduced (thiol, -SH) cysteine residues (2GSH + Ox ↔ GSSG + 2H + , where Ox is an oxidant represented by active oxygen species), may result in oxidative stress [12]. Reversible reduction of disulfide bonds to thiol groups in vivo is controlled by a number of enzymes, including metal-containing ones [7,9,10], whose active sites can be simulated by coordination compounds of d elements.…”

Section: R V Suezov a A V Ereminmentioning

confidence: 99%