Dataset Information

Dioscin-Mediated Autophagy Alleviates MPP⁺-Induced Neuronal Degeneration: An In Vitro Parkinson's Disease Model.

ABSTRACT: Autophagy is a cellular homeostatic process by which cells degrade and recycle their malfunctioned contents, and impairment in this process could lead to Parkinson's disease (PD) pathogenesis. Dioscin, a steroidal saponin, has induced autophagy in several cell lines and animal models. The role of dioscin-mediated autophagy in PD remains to be investigated. Therefore, this study aims to investigate the hypothesis that dioscin-regulated autophagy and autophagy-related (ATG) proteins could protect neuronal cells in PD via reducing apoptosis and enhancing neurogenesis. In this study, the 1-methyl-4-phenylpyridinium ion (MPP⁺) was used to induce neurotoxicity and impair autophagic flux in a human neuroblastoma cell line (SH-SY5Y). The result showed that dioscin pre-treatment counters MPP⁺-mediated autophagic flux impairment and alleviates MPP⁺-induced apoptosis by downregulating activated caspase-3 and BCL2 associated X, apoptosis regulator (Bax) expression while increasing B-cell lymphoma 2 (Bcl-2) expression. In addition, dioscin pre-treatment was found to increase neurotrophic factors and tyrosine hydroxylase expression, suggesting that dioscin could ameliorate MPP⁺-induced degeneration in dopaminergic neurons and benefit the PD model. To conclude, we showed dioscin's neuroprotective activity in neuronal SH-SY5Y cells might be partly related to its autophagy induction and suppression of the mitochondrial apoptosis pathway.

SUBMITTER: Azam S

PROVIDER: S-EPMC9104838 | biostudies-literature | 2022 Apr

REPOSITORIES: biostudies-literature

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Publications

Dioscin-Mediated Autophagy Alleviates MPP<sup>+</sup>-Induced Neuronal Degeneration: An In Vitro Parkinson's Disease Model.

Azam Shofiul S Haque Md Ezazul ME Cho Duk-Yeon DY Kim Joon-Soo JS Jakaria Md M Kim In-Su IS Choi Dong-Kug DK

Molecules (Basel, Switzerland) 20220429 9

Autophagy is a cellular homeostatic process by which cells degrade and recycle their malfunctioned contents, and impairment in this process could lead to Parkinson's disease (PD) pathogenesis. Dioscin, a steroidal saponin, has induced autophagy in several cell lines and animal models. The role of dioscin-mediated autophagy in PD remains to be investigated. Therefore, this study aims to investigate the hypothesis that dioscin-regulated autophagy and autophagy-related (ATG) proteins could protect ...[more]

PMID: 35566180

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Project description:Despite much efforts in the last few decades, the mechanism of degeneration of dopamine (DA) neurons in the substantia nigra (SN) in Parkinson's disease (PD) remains unclear. This represents a major knowledge gap in idiopathic and genetic forms of PD. Among various possible key factors postulated, iron metabolism has been widely suggested to be involved with fueling oxidative stress, a known factor in the pathogenesis of PD. However, the correlation between iron and DA neuron loss, specifically in the SN, has not been described in experimental animal models with great detail, with most studies utilizing rodents and, rarely, non-human primates. In the present study, aiming to gain further evidence of a pathological role of iron in PD, we have examined the correlation of iron with DA neuron loss in a non-human primate model of PD induced by MPTP. We report a significant iron accumulation accompanied by both DA degeneration in the SN and motor deficits in the monkey that displayed the most severe PD pathology and behavioral deficits. The other two monkeys subjected to MPTP displayed less severe PD pathologies and motor deficits, however, their SN iron levels were significantly lower than controls. These findings suggest that high iron may indicate and contribute to heightened MPP+-induced PD pathology in late or severe stages of PD, while depressed levels of iron may signal an early stage of disease. Similarly, using a cell culture preparation, we have found that high doses of ferric ammonium citrate (FAC), a factor known to enhance iron accumulation, increased MPP+-induced cell death in U251 and SH-SY5Y cells, and even in control cells. However, at low dose FAC restored or increased the viability of U251 and SH-SY5Y cells in the absence or presence of MPP+. These observations imply that high levels of iron likely contribute to or heighten MPP+ toxicity in the later stages of PD. While we report reduced iron levels in the earlier stages of MPTP induced PD, the significance of these changes remains to be determined.

Dataset Information

Dioscin-Mediated Autophagy Alleviates MPP⁺-Induced Neuronal Degeneration: An In Vitro Parkinson's Disease Model.

Publications

Dioscin-Mediated Autophagy Alleviates MPP<sup>+</sup>-Induced Neuronal Degeneration: An In Vitro Parkinson's Disease Model.

Similar Datasets

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Dataset Information

Dioscin-Mediated Autophagy Alleviates MPP+-Induced Neuronal Degeneration: An In Vitro Parkinson's Disease Model.

Publications

Dioscin-Mediated Autophagy Alleviates MPP<sup>+</sup>-Induced Neuronal Degeneration: An In Vitro Parkinson's Disease Model.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Dioscin-Mediated Autophagy Alleviates MPP⁺-Induced Neuronal Degeneration: An In Vitro Parkinson's Disease Model.