Alzheimer’s disease is a chronic neurodegenerative disorder characterized by a progressive loss of cognitive and behavioral abilities. Extracellular senile plaques and intracellular neurofibrillary tangles are hallmarks of AD. Researchers aim to analyze the molecular mechanisms underlying AD pathogenesis; however, the therapeutic options available to treat this disease are inadequate. In the past few years, several studies have reported interesting insights about the neuroprotective properties of the polyphenolic compound resveratrol (3, 5, 4′-trihydroxy-trans-stilbene) when used with in vitro and in vivo models of AD. The aim of this review is to focus on the neuroprotective and antioxidant effects of resveratrol on AD and its multiple potential mechanisms of action. In addition, because the naturally occurring forms of resveratrol have a very limited half-life in plasma, a description of potential analogs aimed at increasing the bioavailability in plasma is also discussed.

Resveratrol (trans-3, 5, 4'-trihydroxystilbene) is a polyphenolic phytoalexin known to exhibit antioxidant and neuroprotective effects in several experimental models. Amyloid β peptide (Aβ), a core component of extracellular senile plaques accumulates in the brains of patients with Alzheimer's disease and is related to the development of cognitive impairment and neuronal loss. The present study evaluates the neuroprotective action of resveratrol on Aβ-induced oxidative stress and memory loss. Cultured rat hippocampal H19-7 neuronal cell line was pretreated with 75 μM of resveratrol for 2 hrs followed by 25 μM of Aβ (1-40) for 24 hrs. H19-7 cells treated with Aβ exhibited increased lipid peroxide levels. Enzymatic antioxidants including superoxide dismutase, catalase, glutathione reductase, and non-enzymatic antioxidants such as tocopherol, ascorbic acid and glutathione were decreased in the Aβ treated group when compared to the control group. Aβ treatment also increased the expression of total tau as well as phosphorylated forms of tau (CP13, S202/205; PHF1, S396/404) and decreased the expression of insulin degrading enzyme (IDE), phosphoglycogen synthase kinase 3β involved in Aβ degradation and tau hyper phosphorylation. Expression of PSD-95 and Arc proteins, essential for synaptic maturity and plasticity, was decreased by Aβ treatment. Resveratrol treatment attenuated the accumulation of lipid peroxide levels, up-regulated the antioxidant activities and improved the expression of memory-associated proteins in Aβ treated H19-7 cells. These findings highlight the neuroprotective effect of resveratrol in preventing Aβ-induced oxidative damage and memory loss in vitro.

Resveratrol (3,5,4′-trihydroxy-trans-stilbene) is a polyphenolic phytoalexin that exerts cardioprotective, neuroprotective, and antioxidant effects. Recently it has been shown that obesity is associated with an increase in cerebral oxidative stress levels, which may enhance neurodegeneration. The present study evaluates the neuroprotective action of resveratrol in brain of obese (ob/ob) mice. Resveratrol was administered orally at the dose of 25 mg kg−1 body weight daily for three weeks to lean and obese mice. Resveratrol had no effect on body weight or blood glucose levels in obese mice. Lipid peroxides were significantly increased in brain of obese mice. The enzymatic antioxidants superoxide dismutase, catalase, glutathione peroxidase, glutathione reductase, glucose-6-phosphate dehydrogenase and nonenzymatic antioxidants tocopherol, ascorbic acid, and glutathione were decreased in obese mice brain. Administration of resveratrol decreased lipid peroxide levels and upregulated the antioxidant activities in obese mice brain. Our findings indicate a neuroprotective effect of resveratrol by preventing oxidative damage in brain tissue of obese mice.

Background: TrkA is a transmembrane receptor tyrosine kinase for nerve growth factor. Results: TrkA forms a molecular complex with insulin receptor and IRS-1 to induce Akt and Erk5 phosphorylation. Conclusion: The NGF-TrkA receptor influences insulin signaling. Significance: The TrkA receptor is involved in insulin signaling, and NGF may regulate neuronal glucose uptake as neurons are insulin-insensitive.

The findings of this review highlight the therapeutic potential of combination of nutritionally adequate diet and physical activity in preventing or delaying the symptoms associated with AD pathology.