Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.64 (MPP)
 1,876 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Autophagy is a series of catabolic process mediating the bulk degradation of intracellular proteins and organelles through formation of a double-membrane vesicle, known as an autophagosome, and fusing with lysosome. Autophagy plays an important role of death-survival decisions in neuronal cells, which may influence to several neurodegenerative disorders including Parkinson's disease. Chebulagic acid, the major constituent of Terminalia chebula and Phyllanthus emblica, is a benzopyran tannin compound with various kinds of beneficial effects. This study was performed to investigate the autophagy enhancing effect of chebulagic acid on human neuroblastoma SH-SY5Y cell lines. We determined the effect of chebulagic acid on expression levels of autophago-some marker proteins such as, DOR/TP53INP2, Golgi-associated ATPase Enhancer of 16 kDa (GATE 16) and Light chain 3 II (LC3 II), as well as those of its upstream pathway proteins, AMP-activated protein kinase (AMPK), mammalian target of rapamycin (mTOR) and Beclin-1. All of those proteins were modulated by chebulagic acid treatment in a way of enhancing the autophagy. Additionally in our study, chebulagic acid also showed a protective effect against 1-methyl-4-phenylpyridinium (MPP(+)) - induced cytotoxicity which mimics the pathological symptom of Parkinson's disease. This effect seems partially mediated by enhanced autophagy which increased the degradation of aggregated or misfolded proteins from cells. This study suggests that chebulagic acid is an attractive candidate as an autophagy-enhancing agent and therefore, it may provide a promising strategy to prevent or cure the diseases caused by accumulation of abnormal proteins including Parkinson's disease.
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PMID:Neuroprotective Effect of Chebulagic Acid via Autophagy Induction in SH-SY5Y Cells. 2514 4

Parkinson's disease (PD) is the most common neurodegenerative movement disorder, with current treatment being mainly symptomatic and often accompanied by serious side effects. In search of novel and safe therapeutic agents for PD, natural flavonoids have been shown to exert significant neuroprotective effects. Among them, chrysin (5,7-dihydroxyflavone) has been demonstrated to exhibit anti-oxidative effects to dopaminergic neurons mainly by increasing the expression of Nuclear Factor Erythroid 2 -related factor 2 (NRF2) which reduces intracellular nitric oxide (NO) levels and regulates anti-oxidant pathways. Moreover, chrysin activates Myocyte Enhancer factor 2D (MEF2D), a critical transcription factor involved in dopaminergic survival. It suppresses the MPP-induced upregulation of c-caspase and Bax as well as the downregulation of anti-apoptotic protein Bcl 2. Chrysin also enhances the production of neurotrophic factors, contributing to neuronal survival. Of interest, the combination of chrysin with protocatechuic acid (PCA) has been demonstrated to inhibit neuronal loss in PD animal models. Along with anti-inflammatory properties, chrysin has also been shown to increase dopamine levels in the striatum via monoamino-oxidase B (MAO-B) inhibition while it restores the behavioral deficits in PD animal models. In this review, we discuss the molecular mechanisms that underlie the possible neuroprotective effects of chrysin in PD pathogenesis along with its therapeutic potential.
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PMID:Neuroprotective potential of chrysin in Parkinson's disease: Molecular mechanisms and clinical implications. 3178 48