Modulation of histone deacetylase, the ubiquitin proteasome system, and autophagy underlies the neuroprotective effects of venlafaxine in a rotenone-induced Parkinson's disease model in rats

El-Saiy, Khalid A; Sayed, Rabab H.; El-Sahar, Ayman E.; Kandil, Esraa A.

doi:10.1016/j.cbi.2022.109841

Cited by 29 publications

(21 citation statements)

References 73 publications

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“…Autophagy is used to remove damaged or redundant macroscopic complexes and organelles in eukaryotic cells, and is involved in the occurrence, development, pathogenesis and metastasis of various malignant tumors [24][25]. It has found that the increased level of LC3, Beclin1 protein and the decreased expression of p62 protein indicated the activation of autophagy [26][27].…”

Section: Discussionmentioning

confidence: 99%

Radix Actinidiae chinensis induces autophagy in renal cell carcinoma 786-O and A498 cells by regulating PI3K/AKT/mTOR pathway

Liu

Zhang

2022

Preprint

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Objective: Renal cell carcinoma (RCC) is a malignant tumor. This study investigated the mechanism of Radix Actinidiae chinensis (RAC) inducing autophagy in RCC cell.Methods: Cell viability and IC50 value in 786-O and A498 cells were detected by CCK8 assays. The proliferation, cell cycle, migration and invasion were detected by cloning, flow cytometry and cell invasion assays, respectively. The cell apoptosis, cycle, autophagy and related protein levels were detected by flow cytometry, AOPI assay and western blot, respectively. The number of autophagolysosomes was detected by electron microscopy. In addition, the proteins related to the PI3K/AKT/mTOR pathway were detected by western blot.Results: IC50 values of RAC in 786-O and A498 cells were 14.76 mg/mL and 13.09 mg/mL, respectively. RAC treatment reduced cell viability, proliferation, migration and invasion, blocked the S phase cells, and promoted apoptosis and autophagyin 786-O and A498 cells. It also increased the autophagy-related proteins LC3II/I and Beclin-1, and decreased the level of p62. In addition, RAC activated the levels of apoptosis-related proteins and reduce the levels of PI3K/AKT/mTOR pathway-related proteins. However, the addition of autophagy inhibitor 3-MA attenuated the effect of RAC on apoptosis, autophagy and the expression of related proteins in RCC cells.Conclusion: RAC can induce autophagy in RCC by blocking PI3K/AKT/mTOR pathway, to inhibit the progression of RCC cells.

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Section: Discussionmentioning

confidence: 99%

Radix Actinidiae chinensis induces autophagy in renal cell carcinoma 786-O and A498 cells by regulating PI3K/AKT/mTOR pathway

Liu

Zhang

2022

Preprint

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“…Parkinson disease is characterized by protein aggregates, namely α-synuclein-containing Lewy bodies [ 43 ]. Deterioration of the ubiquitin proteasome system (UPS) and autophagy has been proposed to participate in α-synuclein buildup [ 44 ].…”

Section: Role Of Autophagy In Parkinson Diseasementioning

confidence: 99%

“…Venlafaxine rescued dopaminergic neurons, restored the dopamine levels in the striatum, promoted autophagy, and attenuated the buildup of α-synuclein, resulting in motor recovery in rotenone-induced Parkinson disease model rats [ 44 ].…”

Section: Potential Therapeutic Involvement Of Autophagy In Parkinson ...mentioning

confidence: 99%

Autophagy and Its Association with Genetic Mutations in Parkinson Disease

Erekat

2022

Med Sci Monit

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Parkinson disease is the second most common neurodegenerative disorder, affecting 0.1–0.2% of the general population. It is a progressive debilitating disorder caused by degeneration of dopaminergic neurons in the substantia nigra pars compacta. It is characterized by motor and non-motor symptoms. Parkinson disease can be caused by mutations in genes that encode proteins involved in the autophagic process, resulting in impaired autophagy. Indeed, autophagy has been implicated in the pathogenesis of Parkinson disease, particularly because its impairment causes the buildup of proteins. Thus, this review aims to provide an overview of Parkinson disease-related genetic mutations and their association with autophagy impairment in Parkinson disease, which can be helpful in improving the understanding of the pathogenesis of Parkinson disease, illustrating the potential therapeutic implications of agents that can enhance autophagy in Parkinson disease. Additionally, we will highlight the essential need for the development of highly sensitive and specific assays for gene-based diagnostic biomarkers. Finally, we will provide an overview on the potential gene-based therapeutic approaches for Parkinson disease, which have been most advanced and are associated with the most common targets being alpha-synuclein (SNCA), leucine-rich repeat kinase-2 (LRRK2), and glucocerebrosidase (GBA).

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“…Notably, HGC is a newly developed HDAC6 inhibitor, which improves dopaminergic neuron viability and attenuates behavioral defects in PD modeled cells and animals by accumulation of K28 acetylation of NADH-ubiquinoneoxidoreductase flavoprotein 1 (NDUFV1) and thus maintaining mitochondrial integrity and functions [118]. Interestingly, venlafaxine, in clinically treating depression, was found to inhibit HDAC6 expression and then enhance α-synuclein clearance through the activation of the ubiquitin proteasome system (UPS) and autophagy in a rotenone- induced mice model of PD [119]. Additionally, several probes derived from HDAC6 selective inhibitors may provide powerful tools for investigating HDAC6 in various physiological and pathological conditions.…”

Section: Histone Deacetylase Inhibitors Formentioning

confidence: 99%

“…At least, SIRT2 inhibitor showed neuroprotective effects not only in an α-synuclein-induced Drosophila model of PD, but also in a MPTP-induced mice model of PD [48,88,[123][124][125][126][127][128][129][130][131][132][133]. Besides, HDAC6 inhibitors also showed neuroprotective potentials in several mice models of PD [115][116][117][118][119][120][121][122]. Some isotypes of human histone deacetylases may have neuroprotective roles in PD and nicotinamide, as a Class III HDAC inhibitor against all SIRT1-7, exacerbated the neurotoxic effects in a lactacystin-induced rats model of PD [134].…”

Section: Further Perspectivesmentioning

confidence: 99%

Histone Deacetylases as Epigenetic Targets for Treating Parkinson’s Disease

Li¹,

Gu²,

Lin³

et al. 2022

Preprint

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Parkinson’s disease (PD) is a chronic progressive neurodegenerative disease that increasingly become a global threat for the elder people's health and life. Although there are some drugs in clinic for treating PD, these treatments only can alleviate the symptoms of PD patients but fail in curative therapies. Therefore, seeking other potential mechanisms to develop more effective treatments that can modify the course of PD is still highly desirable. In the last two decades, histone deacetylases as an important group of epigenetic targets in drug discovery have attracted much attention. This review is focused on the current knowledge about histone deacetylases involved in PD pathophysiology and their inhibitors used in PD study. Further perspectives related to small molecules that can inhibit or degrade histone deacetylases to treat PD are also discussed.

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Modulation of histone deacetylase, the ubiquitin proteasome system, and autophagy underlies the neuroprotective effects of venlafaxine in a rotenone-induced Parkinson's disease model in rats

Cited by 29 publications

References 73 publications

Radix Actinidiae chinensis induces autophagy in renal cell carcinoma 786-O and A498 cells by regulating PI3K/AKT/mTOR pathway

Radix Actinidiae chinensis induces autophagy in renal cell carcinoma 786-O and A498 cells by regulating PI3K/AKT/mTOR pathway

Autophagy and Its Association with Genetic Mutations in Parkinson Disease

Histone Deacetylases as Epigenetic Targets for Treating Parkinson’s Disease

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