engleski

p53-mediated neuroprotective effects of natural compounds in oxidative stress conditions

The transcription factor p53 orchestrates cellular response to different types of genotoxic challenges, including oxidative stress (OS). OS is induced by increased accumulation of reactive oxygen species and is tightly linked to the pathogenesis of various neurodegenerative diseases. During OS p53 undergoes posttranslational modifications that trigger its transcriptional activities, leading to activation of pro-apoptotic genes and repression of anti-apoptotic targets. In addition, p53 activity brings neurons into more severe prooxidant state based on the p53-driven activation of pro-oxidant genes and suppression of antioxidant genes. Recent studies suggest that dietary phytochemicals, such as flavonoids, may exert neuroprotective effects by downregulating expression of p53 and acting along p53 pathways. In this chapter we will summarize recent findings related to the p53-mediated neuroprotective effects of natural compounds at the cellular, molecular, and behavioural level in various in vitro and in vivo models of neurodegenerative diseases. Better understanding of the p53-mediated effects in neuroprotection may contribute to the development of more effective pharmacological approaches in OS-driven neurodegeneration.

Alzheimer's disease ; amyotrophic lateral sclerosis ; epigallocatechin-3-gallate ; Huntington's disesase ; mitochondrial DNA (mtDNA) ; oxidative stress ; p53 ; Parkinson's disease ; phosphatase and tensin homolog (PTEN)-induced kinase ; p53-upregulated mediator of apoptosis (PUMA) ; reactive oxygen species (ROS) ; silent information regulator 1 (SIRT1) ; TP-53-induced glycolysis and apoptosis regulator (TIGAR) ; TP53 gene (tumor protein 53)

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