Neuroprotective effects of genistein on SH-SY5Y cells overexpressing A53T mutant α-synuclein

Wu, Huancheng; Hu, Qun-liang; Zhang, Shijun; Wang, Yanmin; Jin, Zhankui; Lv, Ling-Fu; Zhang, Sai; Liu, Zhen-Lin; Wu, Hong-Lian; Cheng, Oumei

doi:10.4103/1673-5374.235250

Cited by 42 publications

(12 citation statements)

References 56 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Previous studies reported that exposure to nM concentrations of rotenone for 24 hours was found to decrease SH-SY5Y cell viability to 50% when compared to untreated cells [29,30]. However, rotenone at higher concentrations were needed to effect cellular viability in our study model, similar to recent studies [31,32]. At lower concentrations, we could not observe any damage.…”

Section: Discussionsupporting

confidence: 88%

The comparison of apoptosis-related protein expressions in neurotoxin-based in vitro Parkinson s Disease models

Kaftan¹,

Armağan²,

Dağcı³

2020

jrp

View full text Add to dashboard Cite

Programmed cell death (apoptosis) is mainly responsible for neuronal damage in neurodegenerative diseases. Thus, inhibition of apoptosis could represent an effective strategy in the prevention of these diseases. In this study, we aimed to compare the apoptotic responses of neurotoxins that are widely used to induce neuronal damage in cell culture studies and help to decide the most suitable experimental model for drug studies that target apoptosis. Cell viability analyses were performed by MTT assay following 1-methyl-4-phenylpyridinium (MPP +), 6-hydroxydopamine (6-OHDA), rotenone and paraquat treatments at three different time points (12, 24, 48h). Pro-apoptotic (Bax, Bad, Bak), anti-apoptotic (Bcl-2, Bcl-xl) protein levels and total caspase-3 protein levels were determined by Western Blotting technique following treatments. As expected, all neurotoxins managed to trigger cell death and apoptotic pathway. On the other hand, each neurotoxin was found to enhance and/or reduce the levels of different proteins that are associated with apoptosis. Due to different responses of apoptosis related proteins to neurotoxins, it can be concluded that the determination of target proteins with a number of protein-binding assays prior to cell culture studies and then deciding an in vitro model are essential while screening newly synthesized drugs that target apoptosis.

show abstract

Section: Discussionsupporting

confidence: 88%

The comparison of apoptosis-related protein expressions in neurotoxin-based in vitro Parkinson s Disease models

Kaftan¹,

Armağan²,

Dağcı³

2020

jrp

View full text Add to dashboard Cite

show abstract

“…In summary, our results demonstrate that genistein can correct HD phenotype in patient-derived cells. Of note, genistein might also be effective in other neurodegenerative diseases, e.g., Alzheimer’s disease (Pierzynowska et al 2019 ), and Parkinson’s disease (Wu et al 2018 ). Therefore, it is tempting to suggest that genistein, acting as an autophagy stimulator, can be considered a potential therapeutic agent for various neurodegenerative diseases that feature accumulation of misfolded proteins.…”

Section: Discussionmentioning

confidence: 99%

Genistein induces degradation of mutant huntingtin in fibroblasts from Huntington’s disease patients

et al. 2019

View full text Add to dashboard Cite

Mutations in the HTT gene, consisting of expansion of CAG triplets, cause the Huntington’s disease (HD), one of the major neurodegenerative disorders. Formation of aggregates of mutant huntingtin (mHTT, the product of the mutant HTT gene) leads to cellular dysfunctions, and subsequent neurodegeneration which manifest clinically as motor abnormalities and cognitive deficits. We recently used immortalized HEK-293 cells expressing the 1st exon of the mutant HTT gene as a cellular model of HD, and showed that the stimulation of autophagy by genistein corrected the mutant phenotype. However, effects of genistein on HD patient-derived cells remained unknown. In this report, we demonstrated that genistein also instigated degradation of mHTT in fibroblasts derived from HD patients. This was assessed as a significant decrease in the levels of HTT in HD fibroblasts measured by Western-blotting, and the disappearance of intracellular mHTT aggregates in cells observed by fluorescent microscopy. Fibroblasts derived from control persons were not affected by genistein treatment. These results indicate that genistein can improve HD phenotype in patient-derived cells, and substantiates the need for further studies of this isoflavone as a potential therapeutic agent.

show abstract

“…It has been demonstrated that GE possesses many physiological and pharmacological properties, ranging from antioxidant, anti-mutagenic and anticancer activities to cardio-protective and immunomodulatory capacities ( Jeon et al, 2014 ; Ekambaram et al, 2016 ; Kang et al, 2016 ; Russo et al, 2016 ). In recent years, a growing number of both clinical and preclinical studies have suggested GE a potential neuroprotective and memory-enhancing drug against neurodegenerative diseases ( Rahman et al, 2012 ; Du et al, 2018 ; Wu et al, 2018 ). It was reported that GE has exhibited the beneficial role against menopause-associated cognitive deficits and neurodegeneration through diminishing oxidative stress ( Xu et al, 2007 ) and high consumption of GE in the diet has health-promoting benefits like memory improvement in volunteers of both genders ( File et al, 2001 ).…”

Section: Introductionmentioning

confidence: 99%

Genistein Ameliorates Scopolamine-Induced Amnesia in Mice Through the Regulation of the Cholinergic Neurotransmission, Antioxidant System and the ERK/CREB/BDNF Signaling

Lü

Yan

et al. 2018

Front. Pharmacol.

View full text Add to dashboard Cite

Genistein (GE) was reported to exert a wide spectrum of biological activities, including antioxidant, anti-inflammatory, anti-mutagenic, anticancer, and cardio-protective effects. In addition, both clinical and preclinical studies have recently suggested GE a potential neuroprotective and memory-enhancing drug against neurodegenerative diseases. The animal model of scopolamine (Scop)-induced amnesia is widely used to study underlying mechanisms and treatment of cognitive impairment in neurodegenerative diseases. However, there is no report about the effects of GE on Scop-induced amnesia in mice. Therefore, the present study was carried out to investigate the beneficial effects and potential mechanism of GE against Scop-induced deficits in mice. The mice were orally pretreated with either GE (10, 20, and 40 mg/kg) or donepezil (1.60 mg/kg) for 14 days. After the pretreatment, the open field test was conducted to assess the effect of GE on the locomotor activity of mice. Thereafter, mice were daily injected with Scop (0.75 mg/kg) intraperitoneally to induce memory deficits and subjected to the cognitive behavioral tests including the Object Location Recognition (OLR) experiment and Morris Water Maze (MWM) task. After the behavioral tests, biochemical parameter assay and western blot analysis were used to examine the underlying mechanisms of its action. The results showed that GE administration significantly improved the cognitive performance of Scop-treated mice in OLR and Morris water maze tests, exerting the memory-enhancing effects. Additionally, GE remarkably promoted the cholinergic neurotransmission and protected against the oxidative stress damage in the hippocampus of Scop-treated mice, as indicated by decreasing AChE activity, elevating ChAT activity and Ach level, increasing SOD activity, lowering the level of MDA and increasing GSH content. Furthermore, GE was found to significantly upregulate the expression levels of p-ERK, p-CREB and BDNF proteins in the hippocampus of Scop-treated mice. Taken together, these results for the first time found that GE exerts cognitive-improving effects in Scop-induced amnesia and suggested it may be a potential candidate compound for the treatment of some neurodegenerative diseases such as Alzheimer’s Disease (AD).

show abstract

Neuroprotective effects of genistein on SH-SY5Y cells overexpressing A53T mutant α-synuclein

Cited by 42 publications

References 56 publications

The comparison of apoptosis-related protein expressions in neurotoxin-based in vitro Parkinson s Disease models

The comparison of apoptosis-related protein expressions in neurotoxin-based in vitro Parkinson s Disease models

Genistein induces degradation of mutant huntingtin in fibroblasts from Huntington’s disease patients

Genistein Ameliorates Scopolamine-Induced Amnesia in Mice Through the Regulation of the Cholinergic Neurotransmission, Antioxidant System and the ERK/CREB/BDNF Signaling

Contact Info

Product

Resources

About