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Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

ABSTRACT: Parkinson's disease (PD) is a progressive neurodegenerative disorder that arises due to a complex and variable interplay between elements including age, genetic, and environmental risk factors that manifest as the loss of dopaminergic neurons. Contemporary treatments for PD do not prevent or reverse the extent of neurodegeneration that is characteristic of this disorder and accordingly, there is a strong need to develop new approaches which address the underlying disease process and provide benefit to patients with this debilitating disorder. Mitochondrial dysfunction, oxidative damage, and inflammation have been implicated as pathophysiological mechanisms underlying the selective loss of dopaminergic neurons seen in PD. However, results of studies aiming to inhibit these pathways have shown variable success, and outcomes from large-scale clinical trials are not available or report varying success for the interventions studied. Overall, the available data suggest that further development and testing of novel therapies are required to identify new potential therapies for combating PD. Herein, this review reports on the most recent development of antioxidant and anti-inflammatory approaches that have shown positive benefit in cell and animal models of disease with a focus on supplementation with natural product therapies and selected synthetic drugs.

SUBMITTER: Leathem A

PROVIDER: S-EPMC9266756 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:Colon cancer (CC) is the third common neoplasm worldwide, and it is still a big challenge for exploring new effective medicine for treating CC. Natural product promoting human health has become a hot topic and attracted many researchers recently. Pectin, a complex polysaccharide in plant cell wall, mainly consists of four major types of polysaccharides: homogalacturonan, xylogalacturonan, rhamnogalacturonan I and II, all of which can be degraded into various pectin oligosaccharides (POS) and may provide abundant resource for exploring potential anticancer drugs. POS have been regarded as a novel class of potential functional food with multiple health-promoting properties. POS have antibacterial activities against some aggressive and recurrent bacterial infection and exert beneficial immunomodulation for controlling CC risk. However, the molecular functional role of POS in the prevention of CC risk and progression remains doubtful. The review focuses on antioxidant and anti-inflammatory roles of POS for promoting human health by regulating some potential oxidative and inflammation-activated pathways, such as ATP-activated protein kinase (AMPK), nuclear factor erythroid-2-related factor-2 (Nrf2), and nuclear factor-?B (NF-?B) pathways. The activation of these signaling pathways increases the antioxidant and antiinflammatory activities, which will result in the apoptosis of CC cells or in the prevention of CC risk and progression. Thus, POS may inhibit CC development by affecting antioxidant and antiinflammatory signaling pathways AMPK, Nrf2, and NF-?B. However, POS also can activate signal transduction and transcriptional activator 1 and 3 signaling pathway, which will reduce antioxidant and anti-inflammatory properties and promote CC progression. Specific structural and structurally modified POS may be associated with their functions and should be deeply explored in the future. The present review paper lacks the important information for the linkage between the specific structure of POS and its function. To further explore the effects of prebiotic potential of POS and their derivatives on human immunomodulation in the prevention of CC, the specific POS with a certain degree of polymerization or purified polymers are highly demanded to be performed in clinical practice.

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Evidence for Oxidative Pathways in the Pathogenesis of PD: Are Antioxidants Candidate Drugs to Ameliorate Disease Progression?

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