Τίτλος:
Neuroprotective potential of chrysin in Parkinson's disease: Molecular mechanisms and clinical implications
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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. © 2019 Elsevier Ltd
Συγγραφείς:
Angelopoulou, E.
Pyrgelis, E.-S.
Piperi, C.
Περιοδικό:
Neurochemistry International
Εκδότης:
Elsevier Ireland Ltd
Λέξεις-κλειδιά:
amine oxidase (flavin containing) isoenzyme B; caspase; chrysin; myocyte enhancer factor 2; neurotrophic factor; protein Bax; transcription factor Nrf2; antioxidant; BCL2 protein, human; chrysin; flavonoid; neuroprotective agent; NFE2L2 protein, human; protein bcl 2; transcription factor Nrf2, antiinflammatory activity; antioxidant activity; cell survival; corpus striatum; dopamine metabolism; dopaminergic nerve cell; drug bioavailability; drug mechanism; drug structure; enzyme inhibition; human; neuroapoptosis; neuroprotection; nonhuman; Parkinson disease; pathogenesis; priority journal; protein expression; Review; animal; metabolism; Parkinson disease, Animals; Antioxidants; Flavonoids; Humans; Neuroprotective Agents; NF-E2-Related Factor 2; Parkinson Disease; Proto-Oncogene Proteins c-bcl-2
DOI:
10.1016/j.neuint.2019.104612
