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

Leathem, Alexander; Ortiz, Tamara; Dennis, Joanne M.; Witting, Paul K.

doi:10.3390/ijms23136923

Cited by 14 publications

(12 citation statements)

References 221 publications

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“…As distinct tyrosine residues determine the substrate specificity of monoamine oxidase B (MAO B), this may further deregulate dopamine metabolism. Additionally, peroxynitrite inactivates glutathione reductase, depleting the intracellular GSH content in substantia nigra [ 8 , 108 , 109 ]. In a rotenone-induced animal model of PD, a natural CB2 receptor agonist β-caryophyllene demonstrated neuroprotective effects.…”

Section: Intracellular Signaling Pathways Induced By Activation Of Cb...mentioning

confidence: 99%

Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

et al. 2022

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In the last few decades, endocannabinoids, plant-derived cannabinoids and synthetic cannabinoids have received growing interest as treatment options in neurodegenerative conditions. In various experimental settings, they have displayed antioxidative, anti-inflammatory, antiapoptotic, immunomodulatory, and neuroprotective effects. However, due to numerous targets and downstream effectors of their action, the cellular and molecular mechanisms underlying these effects are rather complex and still under discussion. Cannabinoids are able to neutralize free radicals and modulate the production of reactive oxygen species and the activity of antioxidative systems acting on CB1 and CB2 cannabinoid receptors. The activation of CB1 receptors stimulates signaling pathways involved in antioxidative defense and survival (such as the phosphoinositide 3-kinase (PI3K)/Akt, mitogen-activated protein kinase (MAPK), and Nrf2 pathways) and regulates glutamatergic signaling, the activation of N-methyl-D-aspartate (NMDA) receptors, calcium influx, and the induction of Ca2+-regulated signaling cascades, whereas the neuroprotective effects mediated by CB2 receptors are due to the suppression of microglial activation and the release of prooxidative and proinflammatory mediators. This review summarizes the main molecular mechanisms and new advances in understanding the antioxidative and neuroprotective effects of cannabinoids. Because of the plethora of possible pharmacological interventions related to oxidative stress and cannabinoid-mediated neuroprotection, future research should be directed towards a better understanding of the interplay between activated signal transduction pathways and molecular targets with the aim to improve treatment options and efficacy by targeting the endocannabinoid system.

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Section: Intracellular Signaling Pathways Induced By Activation Of Cb...mentioning

confidence: 99%

Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

et al. 2022

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“…Selenium, through its incorporation into glutathione peroxidase, combats oxidative stress, thereby potentially mitigating dopaminergic neuron degeneration, a hallmark of PD. [5] Concurrently, selenium’s impact on inflammatory pathways, highlighted by its regulation of cytokine production, aligns with emerging research on PD’s inflammatory underpinnings, including the notable roles of neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) as markers of neuroinflammation. [6,7] This dual capacity underscores the significance of selenium in the neurodegenerative process and supports the investigation into its levels in PD patients.…”

Section: Introductionmentioning

confidence: 93%

Association between Parkinson disease and selenium levels in the body: A systematic review and meta-analysis

Chen,

Hu,

Zhang

et al. 2024

Medicine

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Background: Parkinson disease (PD) is a common neurodegenerative disorder, but its pathogenesis is still not entirely understood. While some trace elements, such as selenium, iron, and copper, are considered pivotal in PD onset due to their role in oxidative stress, the association between selenium concentrations and PD susceptibility remains ambiguous. Methods: A systematic review and meta-analysis was conducted in adherence to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and framed by the Patient, Intervention, Comparison, Outcome paradigm. Data were sourced from 4 prominent electronic databases: PubMed, Embase, Web of Science, and Cochrane Library. Eligible studies must have had a PD case group and a control group, both of which presented data on selenium concentrations. The quality of the studies was assessed using the Newcastle-Ottawa Scale. Results: Of 1541 initially identified articles, 12 studies comprising a total of 597 PD cases and 733 controls were selected for the meta-analysis. Pronounced heterogeneity was observed among these studies. When assessing blood selenium levels, no significant difference was found between patients with PD and the controls. However, when examining the cerebrospinal fluid, selenium levels in PD patients were significantly elevated compared to controls (standard mean difference = 1.21, 95% CI 0.04–2.39, P < .05). Subgroup analyses, sensitivity analyses, and evaluation of publication bias were performed to ensure data robustness. Conclusions: Elevated selenium levels in cerebrospinal fluid may be associated with a higher risk of Parkinson. Further prospective research is required to solidify this potential link and to offer avenues for novel therapeutic interventions or preventive measures.

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“…al. 2012;Dias et al 2013;Crotty et al 2017;Yu et al 2017;Jayanti et al 2021;Wang et al 2021;Leathem et al 2022).…”

Section: Introductionunclassified

Oxidative stress parameters and their relation to motor subtype of Parkinson’s disease and levodopa treatment status

Grofik

Cibulka²,

Oleksakova³

et al. 2023

gpb

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Parkinson's disease (PD) is an oxidative stress-linked neurodegenerative disorder, with the highest prevalence among seniors. The objective of this study were: (1) to analyse levels of following oxidative stress parameters: total antioxidant capacity (TAC), uric acid (UA), total glutathione (tGSH), bilirubin (Bil) and albumin (Alb), in blood of PD patients and healthy controls; (2) to find possible associations of examined oxidative stress parameters with PD subtypes and levodopa treatment status; and (3) to evaluate power and relevance of the aforementioned oxidative stress parameter for the prediction of onset and progression of PD by utilizing Random Forest machine learning (RFML). Oxidative stress parameters were determined in 125 PD patients and 55 healthy controls. Evaluated with frequentist statistics, our data revealed that UA is the only oxidative stress parameter associated with PD. However, when the PD cohort was divided in gender-dependent manner, tGSH and Bil were also significantly associated with PD in subgroup of female patients. RFML rendered no predictive power of any of the tested oxidative stress parameters in respect to PD, its subtypes, and/or status of levodopa treatment. In conclusion, despite the positive association of UA with PD (in complete cohort of PD patients) and of tGSH and Bil with PD but only in female patients, these oxidative stress parameters are of no use in clinical practice due to the lack of the predictive/diagnostic power.

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

Cited by 14 publications

References 221 publications

Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

Intracellular Molecular Targets and Signaling Pathways Involved in Antioxidative and Neuroprotective Effects of Cannabinoids in Neurodegenerative Conditions

Association between Parkinson disease and selenium levels in the body: A systematic review and meta-analysis

Oxidative stress parameters and their relation to motor subtype of Parkinson’s disease and levodopa treatment status

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