Table 1.
Studies showing the protective roles of resveratrol in Alzheimer's disease and Parkinson's disease using different experimental models.
| Disease/Model | Study Modality | Effect of Resveratrol | References |
|---|---|---|---|
| AD | Clinical study | - Resveratrol-activated SIRT1 deacetylated p53, repressing its activity and preventing apoptotic cell death of neurons. | [121] |
| AD | AD transgenic mouse model (3xTg-AD) | - Resveratrol reduced levels of Aβ and p-tau proteins in 3xTg-AD mice. - Resveratrol reduced the levels of amyloidogenic secretase BACE1. - Resveratrol increased AMPK protein levels, and upregulated SIRT1 pathway, including activation of PGC-1α and CREB. - Resveratrol enhanced cognitive function and induced neuroprotection by improving proteostasis to prevent the accumulation of aberrant amyloid and tau proteins. |
[124] |
| AD | Pb-induced oxidative damage and cognitive impairment in mice | - Resveratrol increased nuclear localization and phosphorylation of SIRT1 and increased protein levels of AMPK and PGC-1α. - Resveratrol repressed the Pb-induce amyloidogenic processing decreasing cortical Aβ1-40 levels. - Resveratrol ameliorated spatial learning and memory deficits. |
[125] |
| AD | Amyloid-β protein precursor/presenilin1 (AβPP/PS1) mouse model | - Resveratrol activated SIRT1 and AMPK. - Reduced the amyloid burden and increased mitochondrial complex IV protein levels in mouse brain. - Resveratrol prevented memory loss. |
[126] |
| AD | Amyloid-β protein precursor/presenilin1 (AβPP/PS1) mouse model | - Resveratrol reduced β-amyloid (Aβ) levels. - Resveratrol treatment or SIRT1 activation inhibited autophagy by inhibition of LC3 and Beclin-1 expression. |
[127] |
| AD | Rat model of AD (Aβ1-42 injection into the hippocampus). |
- Resveratrol reversed the reduction in SIRT1 expression. - Resveratrol reversed the reduction in CREB phosphorylation. - Resveratrol recovered neurons from Aβ1–42-induced defects in spatial learning, synaptic plasticity, and memory. |
[128] |
| AD | Aluminum chloride-induced AD rat model | - Selenium-based nanoparticles of resveratrol (RSV-SeNPs) mitigate oxidative stress, neuroinflammation, and mitochondrial dysfunction. - RSV-SeNPs upregulate the expression of SIRT1, clear Aβ peptides, and decrease tau hyperphosphorylation. - RSV-SeNPs reduce the levels of microRNA-134 increasing neurite outgrowth. - RSV-SeNPs improve neurocognitive functions. |
[129] |
| PD | Engraftment of human mesenchymal stem cells in a mouse model of AD. |
- Resveratrol administration can act as an AD-adjuvant therapy to help the engraftment of human mesenchymal stem cells. - Resveratrol action is mediated via SIRT1. - SIRT1 mediates overexpression of neurotrophic factors leading to enhanced neurogenesis, neuron survival, learning, and memory. |
[130, 133] |
| AD | Clinical study | - Resveratrol decreases Aβ levels in cerebrospinal fluid, attenuates neuroinflammation, and induces adaptive immunity in mild to moderate AD patients. | [131] |
| AD | Pilot clinical trial | - Chronic use of resveratrol for 90 days can improve psychomotor speed without enhancing other cognitive functions like memory. | [132] |
| PD | Rat model (6-OHDA-induced PD) | - Resveratrol treatment decreased the levels of COX-2 mRNA and protein. - Resveratrol treatment also decreased the levels of COX-2 mRNA TNF-α mRNA. - Resveratrol alleviated 6-OHDA-induced chromatin condensation and mitochondrial tumefaction of dopaminergic neurons |
[136] |
| PD |
D. melanogaster (parkin mutant) |
- Resveratrol protected against decreased activities of acetylcholinesterase and catalase in parkin-mutant flies. - Resveratrol mitigated the accumulation of oxidative species hydrogen peroxide, nitric oxide and malondialdehyde in parkin-mutant flies. - Resveratrol alleviated locomotor deficits associated with loss of parkin function. |
[137] |
| PD | Cellular models of PD | - In cellular models of PD, resveratrol protected against rotenone-induced apoptosis of SH-SY5Y cells and enhanced degradation of α-synuclein in α-synuclein-expressing PC12 cell lines by induction of autophagy, an AMPK/SIRT1 dependent manner. | [151] |
| PD | In vitro (Human fibroblasts mutant for Parkin 2) | - Resveratrol can enhance mitochondrial respiration through activation of the AMPK/SIRT1/PGC-1α axis. | [152] |
| AD | Neuronal and non-neuronal cells in culture and mouse models | - Resveratrol activates AMPK. - Resveratrol is neuroprotective by decreasing the amyloid proteins and tau hyperphosphorylation. - Resveratrol reduces cognitive impairment in mice. |
[155, 156] |
| AD | Mouse model of AD (Aβ1-42 injection into the brain) | - Intracerebroventricular injection of resveratrol upregulated AMPK/ PGC-1α. - Resveratrol downregulation of markers of inflammation like NF-κB/ IL-1β/ NLRP3. - Resveratrol alleviated Aβ-induced learning and cognitive defects. |
[157] |