Resveratrol alleviates motor and cognitive deficits and neuropathology in the A53T α-synuclein mouse model of Parkinson's disease

Zhang, Lifan; Yu, Xiaolin; Ji, Mei; Liu, Shuying; Wu, Xiaoling; Wang, Yujiong; Liu, Rui‐tian

doi:10.1039/c8fo00964c

Cited by 90 publications

(82 citation statements)

References 62 publications

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“…Alzheimer's disease protective effects in Aβ1-42-treated PC12 cells via reduction of apoptosis and reduction of oxidative status and mitochondrial damage [51] anti-inflammatory effect via suppression of M1 microglia activation, enhancement of Th2 responses and promotion of anti-inflammatory cytokine and SIRT-1 expression [52] reduction of NF-κB signaling in microglia, which plays a pivotal role in Aβdependent neurodegeneration via SIRT-1 activation [53] Parkinson's disease inhibition of α-synuclein aggregation, reduction of the total α-synuclein and oligomers levels and decrease in cytotoxicity, neuroinflammation and oxidative stress in the A53T α-synuclein mouse model of PD in a dose-dependent manner [54] modulation of the MALAT1/miR-129/SNCA signaling pathway via an increase in TH+ cell number and miR-129 expression and decrease in expression of SNCA and MALAT1 by blocking the transcription of its promoter [55] neuroprotective effect through mitochondria dynamics modulation and upregulation of autophagic flux associated with MEK/extracellular signal-regulated kinase signaling pathway [56] Huntington's disease significant improvement of motor coordination and learning through enhancement of expression of mitochondrial-encoded electron transport chain genes in YAC128 mice, related to increased activation of SIRT-1…”

Section: Condition Effects Of Resveratrol Administration Referencesmentioning

confidence: 99%

The Stemness of Human Ovarian Granulosa Cells and the Role of Resveratrol in the Differentiation of MSCs—A Review Based on Cellular and Molecular Knowledge

Józkowiak

Hutchings

Jankowski

et al. 2020

Cells

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Ovarian Granulosa Cells (GCs) are known to proliferate in the developing follicle and undergo several biochemical processes during folliculogenesis. They represent a multipotent cell population that has been differentiated to neuronal cells, chondrocytes, and osteoblasts in vitro. However, progression and maturation of GCs are accompanied by a reduction in their stemness. In the developing follicle, GCs communicate with the oocyte bidirectionally via gap junctions. Together with neighboring theca cells, they play a crucial role in steroidogenesis, particularly the production of estradiol, as well as progesterone following luteinization. Many signaling pathways are known to be important throughout the follicle development, leading either towards luteinization and release of the oocyte, or follicular atresia and apoptosis. These signaling pathways include cAMP, PI3K, SMAD, Hedgehog (HH), Hippo and Notch, which act together in a complex manner to control the maturation of GCs through regulation of key genes, from the primordial follicle to the luteal phase. Small molecules such as resveratrol, a phytoalexin found in grapes, peanuts and other dietary constituents, may be able to activate/inhibit these signaling pathways and thereby control physiological properties of GCs. This article reviews the current knowledge about granulosa stem cells, the signaling pathways driving their development and maturation, as well as biological activities of resveratrol and its properties as a pro-differentiation agent.

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Section: Condition Effects Of Resveratrol Administration Referencesmentioning

confidence: 99%

The Stemness of Human Ovarian Granulosa Cells and the Role of Resveratrol in the Differentiation of MSCs—A Review Based on Cellular and Molecular Knowledge

Józkowiak

Hutchings

Jankowski

et al. 2020

Cells

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“…However, increasing cAMP levels via the Epac pathway retards the clearance of autophagy substrates and inhibits α-synuclein clearance, and enhances polyglutamine aggregation in the Parkinson's disease (PD) mouse model [237]. Intriguingly, RSV rescues mutant polyglutamine cytotoxicity [118] and alleviates motor and cognitive deficits in the A53T αsynuclein mouse model of PD [238], whereas SIRTuin inhibition also rescues polyglutamine cytotoxicity [239], and PD [240] and motor deficits after peripheral nerve injury [241]. Similarly, SIRT1 inhibits p53 [242], a known anti-tumor protein, and RSV is known to exert anti-cancer effects through p53 activation [13,243].…”

Section: Rsv Is Also An Indirect Inhibitor Of Sirt1mentioning

confidence: 99%

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

2020

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Unlike widely perceived, resveratrol (RSV) decreased the average lifespan and extended only the replicative lifespan in yeast. Similarly, although not widely discussed, RSV is also known to evoke neurite degeneration, kidney toxicity, atherosclerosis, premature senescence, and genotoxicity through yet unknown mechanisms. Nevertheless, in vivo animal models of diseases and human clinical trials demonstrate inconsistent protective and beneficial effects. Therefore, the mechanism of action of RSV that elicits beneficial effects remains an enigma. In a previously published work, we demonstrated structural similarities between RSV and tyrosine amino acid. RSV acts as a tyrosine antagonist and competes with it to bind to human tyrosyl-tRNA synthetase (TyrRS). Interestingly, although both isomers of RSV bind to TyrRS, only the cis-isomer evokes a unique structural change at the active site to promote its interaction with poly-ADPribose polymerase 1 (PARP1), a major determinant of cellular NAD +-dependent stress response. However, retention of trans-RSV in the active site of TyrRS mimics its tyrosine-bound conformation that inhibits the autopoly-ADP-ribos(PAR)ylation of PARP1. Therefore, we proposed that cis-RSV-induced TyrRS-regulated auto-PARylation of PARP1 would contribute, at least in part, to the reported health benefits of RSV through the induction of protective stress response. This observation suggested that trans-RSV would inhibit TyrRS/PARP1mediated protective stress response and would instead elicit an opposite effect compared to cis-RSV. Interestingly, most recent studies also confirmed the conversion of trans-RSV and its metabolites to cis-RSV in the physiological context. Therefore, the finding that cis-RSV and trans-RSV induce two distinct conformations of TyrRS with opposite effects on the auto-PARylation of PARP1 provides a potential molecular basis for the observed dichotomic effects of RSV under different experimental paradigms. However, the fact that natural RSV exists as a diastereomeric mixture of its cis and trans isomers and cis-RSV is also a physiologically relevant isoform has not yet gained much scientific attention. Keywords Resveratrol (RSV). Aminoacyl-tRNA synthetases (aaRSs). Tyrosyl-tRNA synthetase (YARS. TyrRS). Nicotinamide adenine nucleotide (NAD +). Poly-ADP-ribose polymerase (PARP). Sirtuins (SIRT). AMP-activated protein kinase (AMPK). Nicotinamide (NAM) GeroScience

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“…The object recognition test was performed as previously described with some modifications (Lueptow, 2017; Zhang et al, 2018). Briefly, mice were individually habituated to the behavioural arena (50 cm × 50 cm × 25 cm white plastic box, empty) for 5 min 1 day before the test was initiated.…”

Section: Methodsmentioning

confidence: 99%

Vaccines targeting the primary amino acid sequence and conformational epitope of amyloid‐β had distinct effects on neuropathology and cognitive deficits in EAE/AD mice

Zhu

Liu

et al. 2020

British J Pharmacology

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Background and Purpose:Immunotherapeutic intervention is one of the most promising strategies for the prevention and treatment of Alzheimer's disease (AD). Although they showed great success in AD mouse models, the clinical trials of many immune approaches failed due to low efficacy and safety. Thus, an animal model which can show the potential side effects of vaccines or antibodies is urgently needed. In this study, we generated EAE/AD mice by crossing APP/PS1 mice with experimental autoimmune encephalomyelitis (EAE) mice. We then investigated the efficacy and safety of two vaccines: the immunogens of which were Aβ1-42 aggregates (Aβ42 vaccine) and an oligomer-specific conformational epitope (AOE1 vaccine), respectively.Experimental Approach: EAE/AD mice were immunized with the Aβ42 vaccine or AOE1 vaccine five times at biweekly intervals. After the final immunization, cognitive function was evaluated by the Morris water maze, Y maze, and object recognition tests.Neuropathological changes in the mouse brains were analysed by immunohistochemistry and ELISA. Key Results:In contrast to previous findings in conventional AD animal models, Aβ42 immunization promoted neuroinflammation, enhanced Aβ levels and plaque burden, and failed to restore cognitive deficits in EAE/AD mice. By contrast, AOE1 immunization dramatically attenuated neuroinflammation, reduced Aβ levels, and improved cognitive performance in EAE/AD mice. Conclusion and Implications:These results suggest that the EAE/AD mouse model can exhibit the potential side effects of AD immune approaches that conventional AD animal models fail to display. Furthermore, strategies specifically targeting Aβ oligomers may be safe and show clinical benefit for AD treatment.

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Resveratrol alleviates motor and cognitive deficits and neuropathology in the A53T α-synuclein mouse model of Parkinson's disease

Abstract: Resveratrol exerts neuroprotective effects on the A53T α-synuclein mouse model of Parkinson's disease.

Cited by 90 publications

References 62 publications

The Stemness of Human Ovarian Granulosa Cells and the Role of Resveratrol in the Differentiation of MSCs—A Review Based on Cellular and Molecular Knowledge

The Stemness of Human Ovarian Granulosa Cells and the Role of Resveratrol in the Differentiation of MSCs—A Review Based on Cellular and Molecular Knowledge

Towards resolving the enigma of the dichotomy of resveratrol: cis- and trans-resveratrol have opposite effects on TyrRS-regulated PARP1 activation

Vaccines targeting the primary amino acid sequence and conformational epitope of amyloid‐β had distinct effects on neuropathology and cognitive deficits in EAE/AD mice

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