Targeting the Interplay Between Autophagy and the Nrf2 Pathway in Parkinson’s Disease with Potential Therapeutic Implications

Biomolecules, Journal Year: 2025, Volume and Issue: 15(1), P. 149 - 149

Published: Jan. 19, 2025

Parkinson’s disease (PD) is a prevalent neurodegenerative disorder marked by the progressive degeneration of midbrain dopaminergic neurons and resultant locomotor dysfunction. Despite over two centuries recognition as chronic disease, exact pathogenesis PD remains elusive. The onset progression involve multiple complex pathological processes, with dysfunctional autophagy elevated oxidative stress serving critical contributors. Notably, emerging research has underscored interplay between in pathogenesis. Given limited efficacy therapies targeting either dysfunction or stress, it crucial to elucidate intricate mechanisms governing their develop more effective therapeutics. This review overviews role nuclear factor erythroid 2-related 2 (Nrf2), pivotal transcriptional regulator orchestrating cellular defense against these processes. By elucidating key processes PD, this will deepen our comprehensive understanding multifaceted underlying may uncover potential strategies for its prevention treatment.

Language: Английский

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The Expanding Burden of Neurodegenerative Diseases: An Unmet Medical and Social Need

Aging and Disease, Journal Year: 2024, Volume and Issue: unknown, P. 0 - 0

Published: Jan. 1, 2024

Neurodegenerative diseases, particularly Alzheimer's disease and other dementias as well Parkinson's disease, are emerging profoundly significant challenges burdens to global health, a trend highlighted by the most recent Global Burden of Disease (GBD) 2021 studies. This growing impact is closely linked demographic shift toward an aging population potential long-term repercussions COVID-19 pandemic, both which have intensified prevalence severity these conditions. In this review, we explore several critical aspects complex issue, including increasing burden neurodegenerative unmet medical social needs within current care systems, unique amplified posed strategies for enhancing healthcare policy practice. We underscore urgent need cohesive, multidisciplinary approaches across medical, research, domains effectively address thereby improving quality life patients their caregivers.

Language: Английский

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Revolutionizing Parkinson’s treatment: Harnessing the potential of intranasal nanoemulsions for targeted therapy

Drug Delivery and Translational Research, Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 8, 2025

Language: Английский

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Parkinson’s disease detection from speech using combination of empirical wavelet transform and Hilbert transform

International Journal of Speech Technology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Language: Английский

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Regulation of polyamine interconversion enzymes affects α-Synuclein levels and toxicity in a Drosophila model of Parkinson's disease

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: March 10, 2025

Abstract Parkinson’s Disease (PD) is a prevalent neurodegenerative disorder with the accumulation and aggregation of alpha-synuclein (α-Syn) as central pathological hallmark. Misfolding α-Syn disrupts cellular homeostasis, hinders mitochondrial function, activates neuroinflammatory responses, ultimately resulting in neuronal death. Recent biomarker research indicated notable increase serum concentrations three L-ornithine-derived polyamines (PAs): putrescine, spermidine, spermine, each correlating progression PD its clinical subtypes. However, role PA pathways pathology poorly understood; it unclear whether elevated are linked to pathology, or they represent secondary effect. In this study, we targeted PAs through RNAi knockdown different PA-interconversion enzymes (PAIE) Drosophila melanogaster model that overexpresses human, wild-type α-Syn. Our findings reveal significant impact on both lifespan motility PD-model flies when crucial PAIE, such ornithine decarboxylase 1 (ODC1), spermidine synthase (SRM), spermidine/spermine N1-acetyltransferase (SAT1), spermine oxidase (SMOX) targeted. The overexpression SAT1 SMOX had positive, enduring effects fly lifespan. Additionally, noted alterations ⍺-Syn protein levels PAIE either knocked down overexpressed. These underscore their potential targeting modulate mitigate neurodegeneration PD.

Language: Английский

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Xifeng Jiannao pill mitigates MPTP-induced neuronal apoptosis by reducing inflammation and oxidative stress via MAPK signaling

Metabolic Brain Disease, Journal Year: 2025, Volume and Issue: 40(4)

Published: April 4, 2025

Language: Английский

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Parkinson’s disease: Public health interventions to mitigate associated stigma

Annals of Movement Disorders, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 14, 2025

Abstract Parkinson’s disease (PD) is a progressive neurodegenerative that primarily manifests as movement disorder. It significantly affects the quality of life individuals, who often experience stigma, disability, and social isolation. These outcomes are largely attributed to widespread myths misconceptions surrounding disease, leading negative consequences in workplaces, public interactions, mental health. Therefore, it crucial raise awareness about PD, strengthen peer networks, foster supportive community environments, ensure healthcare professionals trained provide empathetic, patient-centered care. In conclusion, this study underscores indispensable need for comprehensive, multi-faceted approach address challenges faced by individuals with PD.

Language: Английский

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Nonclinical Preventive Measures of Parkinson's Disease (PD): Identifying Key Lifestyle, Demographic, and Environmental Factors

Research Square (Research Square), Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 27, 2025

Parkinson’s disease (PD) is a neurodegenerative disorder with rising global prevalence. While 15–25% of cases are hereditary, the rest attributed to exogenous factors, such as environmental exposures and lifestyle choices. This study explores relationships between various environmental, lifestyle, health-related factors PD risk via data from Fox Insight database analyzes descriptive statistics, logistic regression, predictive modeling techniques. Key findings show that older age, male sex, lower BMI, unemployment (including both retired unemployed individuals), occupational pesticide exposure increase PD. Interestingly, higher BMI was associated reduced PD, suggesting potential protective effect, althoughthis may be influenced by reverse causality. Additionally, vigorous physical activity found linked an increased which could also reflect causality, where individuals diagnosed their levels in response condition. These results highlight important modifiable for prevention suggest areas further research, particularly understanding complex interactions among exposures, onset.

Language: Английский

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Nonmotor Symptom Changes and Their Association With Falls Among Parkinson's Disease Patients Undergoing Deep Brain Stimulation: A 1‐Year Cohort Study

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(3)

Published: Feb. 28, 2025

ABSTRACT Objectives Fall severely affects the quality of life Parkinson's disease (PD) patients. Subthalamic nucleus (STN) deep brain stimulation (DBS) is an effective treatment for PD motor symptoms (MS), but DBS increased risk falls in some studies and has mixed effects on nonmotor (NMS). However, link between NMS falls, how influences this relationship, remain unclear. This study investigated changes before after STN‐DBS, longitudinal association falls. Methods The included 136 patients undergoing STN‐DBS April 2020 February 2022. Data were collected preoperatively, at 6 months, 12 months postoperatively. Assessments MS via Unified Disease Rating Scale‐III (UPDRS‐III) Nonmotor Symptoms Scale (NMSS). We used Friedman chi‐square tests to assess Specific circumstances assessed through structured interviews. Generalized estimating equations (GEE) explore associations fall occurrence, as well interaction occurrence. Results Significant improvements ( p < 0.01) observed all NMSS domains except gastrointestinal, with no change there significant both locations where occurred whether freezing gait was present among falling 0.01). GEE analysis revealed mood/cognition = 0.044), gastrointestinal 0.027), urinary 0.007), interactions these 0.05). Conclusions NMS, particularly mood/cognition, symptoms, their MS, are associated underscoring need targeted prevention strategies.

Language: Английский

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Genetic study of the NUS1 gene variants in Han Chinese patients with Parkinson’s disease

Ageing and Neurodegenerative Diseases, Journal Year: 2025, Volume and Issue: unknown

Published: April 28, 2025

Aim: Parkinson’s disease (PD) is the second most common progressive neurodegenerative linked to genetic and other factors. The NUS1 dehydrodolichyl diphosphate synthase subunit gene (NUS1) variants were reported be associated with PD. In this PD-control cohort, we aimed explore potential role of in Methods: A cohort 512 Han Chinese sporadic PD patients 516 ethnically age-matched controls underwent clinical evaluation. Peripheral blood samples then collected, whole-exome sequencing was performed. PD-related identified through screening verified using Sanger sequencing, further classified, subsequently analyzed by bioinformatics analysis tools. Statistical conducted assess association between Results: Three heterozygous missense variants, including c.127G>T (p.Ala43Ser, rs1327892878), c.487G>C (p.Asp163His, rs369403261), c.537T>A (p.Asp179Glu, rs28362519), identified. Two rare c.487G>C, exclusively found patients, while low-frequency variant detected both controls. Combined analysis, a potentially pathogenic may exert risk, though no significant shown statistical (all P > 0.05). Conclusion: Our findings suggested that seem not cause monogenic PD, like may, at most, susceptibility

Language: Английский

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