Resveratrol protects against Alzheimer's disease
Neuroprotective effect of sirtuin activation has been confirmed
in mice with Alzheimer's disease
LifeSciencesToday based on the materials of the Universitat de Barcelona:
UB researchers corroborate the neuroprotective effects of Sirtuin 1 activation on mice with Alzheimer’s diseaseScientists at the University of Barcelona (Universitat de Barcelona, UB) have described a mechanism that plays a key role in the development of Alzheimer's disease.
According to an article by Porquet et al. Neuroprotective Role of Trans-Resveratrol in a Murine Model of Familial Alzheimer's Disease, published in the Journal of Alzheimer's Disease, activation of the Sirtuin 1 protein in mice with a model of the hereditary form of this neurodegenerative disease has a neuroprotective effect. A study by David Porquet, PhD, and his colleagues describes for the first time the molecular pathway of Sirtuin 1 in a mouse model.
A group of mice were fed resveratrol, a natural polyphenolic compound found in grapes and red wine. The genetically modified mice used in these experiments develop a familial form of Alzheimer's disease, a hereditary neurodegenerative disease with an early onset, accounting for 5% of all cases of dementia. The dose of resveratrol was equivalent to that prescribed in the form of dietary supplements, and the animals received it for 10 months. Then, the results of resveratrol effects on cognitive functions and neuronal tissues obtained in this group of animals were compared with the results obtained in control mice that did not receive any additives.
Mice of the AbetaPP/PS1 line (amyloid-beta protein precursor/presenilin 1) demonstrate enhanced neuropathological signs of a disease close to the hereditary form of Alzheimer's disease. Alzheimer's disease is a neurodegenerative process that causes severe cognitive impairment; it is characterized by the accumulation of beta–amyloid protein and hyperphosphorylated forms of tau, as well as oxidative and inflammatory processes in the brain. Since there is no effective therapy for Alzheimer's disease, scientists are making significant efforts to understand the biochemical pathways involved in its development. The polyphenol resveratrol induces the expression and activation of several neuroprotective pathways, including the Sirtuin1 and AMPK pathways. The aim of this work was to evaluate the effect of oral resveratrol on AbetaPP/PS1 mice with an Alzheimer's disease model. According to estimates based on object recognition tests, long-term treatment with resveratrol significantly prevented memory loss. In addition, resveratrol reduced amyloid levels and increased the levels of mitochondrial complex IV proteins in the brains of mice. These protective effects of resveratrol are mainly mediated by increased activation of the Sirtuin 1 and AMPK pathways. However, an increase was also observed in the expression of IL1beta and TNF genes, indicating that resveratrol contributes to changes in inflammatory processes, although no changes were found in other key players of the oxidative stress pathway. Taken together, these results show that resveratrol is able to weaken the pathological process occurring in the hippocampus of AbetaPP/PS1 mice and prevent memory loss. (Photo: Universitat de Barcelona)"The results showed that resveratrol improved short-term memory and stopped the accumulation of senile plaques and the formation of tau protein, two of the most characteristic signs of this disease," explains Merce Pallas, professor of the Department of Pharmacology and Therapeutic Chemistry from the UB Aging and Neurodegeneration research group.
Scientists have studied which mechanisms are activated during this process. In particular, they focused on Sirtuin 1, a protein involved in the aging process.
"We used resveratrol because it is believed that part of its positive effects is due to an increase in the activity of sirtuin. Although sirtuin levels were lowered, its activity was increased," Pallas adds.
Surprisingly, the researchers observed an increase in other intracellular mechanisms. Thus, "the beneficial effect of resveratrol enhances all these mechanisms and the function of mitochondria," the scientist concludes.
According to Professor Pallas, the sirtuin pathway may be a good therapeutic target for the treatment of Alzheimer's disease. The study proved that the regulation of this pathway, in this case resveratrol, changes the development of Alzheimer's disease in a mouse model of the hereditary form of this disease.
Sirtuin and agingOne of the previous studies of this group has already proved the important role of Sirtuin 1 in aging.
"We prescribed the same treatment with resveratrol to genetically modified mice with accelerated aging and observed an increase in their life expectancy, which was associated with the activation of sirtuin," emphasizes Professor Pallas.
To understand whether resveratrol is able to protect mitochondria, additional research is needed.
"If we confirm the key role of the interaction of mitochondria and sirtuin, activation of sirtuin with resveratrol can probably protect mice receiving high–fat foods characterized by mitochondrial dysfunction," the researcher concludes.
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