Resveratrol Induces Brain Resilience Against Alzheimer Neurodegeneration Through Proteostasis Enhancement

“…Here, we found that Aβ could hinder cell viability and promote cell apoptosis, inflammation response, and oxidative stress, suggesting that the use of Aβ-induced cell injury to construct an AD cell model in vitro was successful. Besides, Res could alleviate Aβ-induced cell injury, which was consistent with previous research results [23–25].…”

“…These findings are consistent with previous studies of brain ischemia, Parkinson’s disease, and other pathological conditions showing that treatment with RV activates the NFE2l2/ARE pathway [82,83]. Furthermore, RV has been proven to activate SIRT1 through the metabolic sensor AMPK, as indicated above, which is consistent with findings in animal studies [15]. Similarly, the increase in CAT expression is consistent with some animal and human studies showing an increase in both activity and expression of this enzyme as a consequence of RV treatment [84] or SIRT1 overexpression [85].…”

“…In particular, modulation of gene expression of important anti-aging ( SIRT1 , SIRT3 , VPS13C ) and antioxidant ( CAT , CCS , GSTZ1 , NFE2L2 , SOD2 ) genes by RV seems to be partly contributing to its mechanism of action. The fact that protective mechanisms of RV are activated in cells from both healthy and diseased AD donors is in agreement with the activation of protective mechanisms against aberrant proteostasis in both wild-type and AD transgenic mice after chronic treatment with RV [15]. In that last study, we found that RV mechanisms yielded a strong neuroprotection against memory loss and AD pathology in transgenic mice and cognitive enhancement in wild-type mice.…”

“…While the exact mechanisms involved are not clear, one may speculate that different nutraceutical compounds probably have unique and often small effects that are in opposition to brain aging, and when combined in an individually adjusted fashion, these compounds activate a broad enough range of synergistically interacting metabolic pathways that then restore brain resources and reverse brain biological aging. This suggestion is consistent with the known ability of nutraceuticals to affect a highly evolutionarily conserved nutrient-sensing pathway linked to aging [ 287 , 288 , 337 ] and lifespan [ 285 , 286 ]; prevent or slow the progression of a wide variety of illnesses [ 90 , 283 , 284 ], including neurodegeneration [ 289 , 290 , 291 , 337 ]; improve cerebral blood flow and antioxidant capacity [ 338 , 339 ]; and, additionally, affect the central circadian clock in the brain via sirtuins [ 134 , 292 ], which are also linked to the regulation of aging [ 9 , 177 , 293 , 294 ]. In this regard, as has been proposed by Nur et al [ 284 ], nutraceuticals could even be considered “epidrugs”.…”