Neuroprotective effects of resveratrol against beta-amyloid-induced neurotoxicity in rat hippocampal neurons: involvement of protein kinase C. Br J Pharmacol

Department of Psychiatry, Douglas Hospital Research Centre, McGill University, 6875 Boulevard LaSalle, Montreal, Québec, Canada H4H 1R3.
British Journal of Pharmacology (Impact Factor: 4.84). 04/2004; 141(6):997-1005. DOI: 10.1038/sj.bjp.0705688
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1. Resveratrol, an active ingredient of red wine extracts, has been shown to exhibit neuroprotective effects in several experimental models. 2. The present study evaluated the neuroprotective effects of resveratrol against amyloid beta(Abeta)-induced toxicity in cultured rat hippocampal cells and examined the role of the protein kinase C (PKC) pathway in this effect. 3. Pre-, co- and post-treatment with resveratrol significantly attenuated Abeta-induced cell death in a concentration-dependent manner, with a concentration of 25 microm being maximally effective. 4. Pretreatment (1 h) of hippocampal cells with phorbol-12-myristate-13-acetate, a PKC activator, at increasing concentrations (1-100 ng x ml(-1)), resulted in a dose-dependent reduction in Abeta-induced toxicity, whereas the inactive 4alpha-phorbol had no effect. 5. Pretreatment (30 min) of hippocampal cells with GF 109203X (1 microm), a general PKC inhibitor, significantly attenuated the neuroprotective effect of resveratrol against Abeta-induced cell death. 6. Treatment of hippocampal cells with resveratrol (20 microm) also induced the phosphorylation of various isoforms of PKC leading to activation. 7. Taken together, the present results indicate that PKC is involved in the neuroprotective action of resveratrol against Abeta-induced toxicity.

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Available from: Wen Hua Zheng, Sep 30, 2015
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    • "Rsv and Quercetin, which are known activators of Sirt1 (NAD + -dependent histone deacetylase) and AMPK (Cantó et al., 2010), have the ability to block agedependent decline in locomotor activity and memory (Valenzano et al., 2006). Rsv delays axonal degeneration after injury (Araki et al., 2004), blocks accumulation of A peptide in vitro (Han et al., 2004), and provides protection from brain ischemia in both adult and neonatal rodents (Wang et al., 2002). Accordingly, Rsv is currently being evaluated in clinical trials of patients with Alzheimer's disease. "
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    ABSTRACT: Herpes simplex virus type 1 (HSV-1) is ubiquitous and is able to establish a lifelong persistent latent infection in neurons of infected individuals. It has been estimated that in approximately 70% of the population over 50 years old, the virus enters the brain and infects neurons, and possibly undergoes recurrent reactivation episodes during lifetime, especially in immunodepressed individuals. We previously showed that the sensors AMP-dependent kinase (AMPK) and Sirtuin 1 (Sirt1), involved in survival pathways and neuroprotection, were affected during the course of HSV-1 infection. To evaluate if natural activators of the AMPK/Sirt1 axis, such as Resveratrol and Quercetin could reduce viral propagation and/or counteract the effects of neuronal infection we analyzed progeny virion production, neuronal viability and neurodegenerative events during HSV-1 infection. We found that the activators of AMPK/Sirt1 axis, increased the viability of infected neurons, significantly reduced the viral titer in the supernatant and the expression of viral genes. More importantly, pretreatment of neurons with Resveratrol or Quercetin significantly reduced the levels of caspase-3 cleaved- and hyperphosphorylated tau associated with HSV-1 infection. These results suggest that activators of the AMPK/Sirt1 axis could be potentially useful in reducing the risk of HSV-1 productive infection in neurons and the cellular damage associated with reactivation episodes. Copyright © 2015. Published by Elsevier B.V.
    Virus Research 05/2015; 205. DOI:10.1016/j.virusres.2015.05.015 · 2.32 Impact Factor
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    • "Moreover, resveratrol slightly decreased the phosphorylation of PKC-d, but did not affect the phosphorylation of PKCí µí»¼/í µí»½II, PKC-í µí¼‡ (Ser916), and PKC-í µí¼ƒ (Thr538), suggesting that PKC-í µí»¿ (Thr505) was involved in the neuroprotective effects of resveratrol. In short, the PKC pathway played a major role in the neuroprotective-neurorescuing properties of resveratrol against Aí µí»½-induced toxicity in hippocampal neurons [43]. "
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    ABSTRACT: Alzheimer's disease (AD) is the most common cause of dementia, but there is no effective therapy till now. The pathogenic mechanisms of AD are considerably complex, including Aβ accumulation, tau protein phosphorylation, oxidative stress, and inflammation. Exactly, resveratrol, a polyphenol in red wine and many plants, is indicated to show the neuroprotective effect on mechanisms mostly above. Recent years, there are numerous researches about resveratrol acting on AD in many models, both in vitro and in vivo. However, the effects of resveratrol are limited by its pool bioavailability; therefore researchers have been trying a variety of methods to improve the efficiency. This review summarizes the recent studies in cell cultures and animal models, mainly discusses the molecular mechanisms of the neuroprotective effects of resveratrol, and thus investigates the therapeutic potential in AD.
    BioMed Research International 11/2014; 2014:350516. DOI:10.1155/2014/350516 · 3.17 Impact Factor
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    • "The activation of protein kinase C (PKC) may stimulate α-secretase and then non-amyloidogenic pathway in APP processing, resulting in a reduction in the production of Aβ [53]. Our group reported that dihydrochloride3-(1-[3-(dimethylamino) propyl]-1H-indol-3yl)-4- (1H-indol-3-yl)-1H-pyrrole-2,5-dione (GF 109203X), a PKC inhibitor, attenuated the neuroprotective effects of resveratrol against Aβinduced toxicity in hippocampal cell cultures [38]. Moreover, Western blot data suggested that resveratrol (20–30 μM) induced the phosphorylation of the PKC delta (δ) isoform, whose inhibition is required for initiation of the apoptotic pathway [54]. "
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    ABSTRACT: Low-to-moderate red wine consumption appeared to reduce age-related neurological disorders including macular degeneration, stroke, and cognitive deficits with or without dementia. Resveratrol has been considered as one of the key ingredients responsible for the preventive action of red wine since the stilbene displays a neuroprotective action in various models of toxicity. Besides its well documented free radical scavenging and anti-inflammatory properties, resveratrol has been shown to increase the clearance of beta-amyloid, a key feature of Alzheimer's disease, and to modulate intracellular effectors associated with oxidative stress (e.g. heme oxygenase), neuronal energy homeostasis (e.g. AMP kinase), program cell death (i.e. AIF) and longevity (i.e. sirtuins). This article summarizes the most recent findings on mechanisms of action involved in the protective effects of this multi target polyphenol, and discusses its possible roles in the prevention of various age-related neurological disorders. This article is part of a Special Issue entitled: Resveratrol: Challenges in translating pre-clinical findings to improved patient outcomes.
    Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease 10/2014; DOI:10.1016/j.bbadis.2014.09.011 · 4.88 Impact Factor
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