Possible linking and treatment between Parkinson’s disease and inflammatory bowel disease: a study of Mendelian randomization based on gut–brain axis

Journal of Translational Medicine, Journal Year: 2025, Volume and Issue: 23(1)

Published: Jan. 11, 2025

Mounting evidence suggests that Parkinson's disease (PD) and inflammatory bowel (IBD) are closely associated becoming global health burdens. However, the causal relationships common pathogeneses between them uncertain. Furthermore, they uncurable. Thus, we aimed to identify novel therapeutic targets shared based on their pathophysiological mechanisms in gut–brain-axis (GBA). A meta-analysis bidirectional Mendelian randomization (MR) utilizing various datasets was performed estimate relationship. Then, pleiotropic analysis under composite null hypothesis (PLACO) with functional mapping combined annotation of genetic associations (FUMA) were conducted genes. Next, blood, brain intestine expression quantitative trait locus (eQTL) taken perform drug-target MR finding genes two diseases. Colocalization ensured eQTLs corresponding gene colocalized disease. Enrichment protein‒protein interaction (PPI) network done explore pathogenesis pathways. Genes passed all regarded as drug targets. Our revealed relationship diseases, ORs for PD IBD, CD, UC (1.050 [95% CI 1.014–1.086], 1.044 0.995–1.095], 1.063 1.016–1.120]); (1.003 0.973–1.034], 1.035 1.004–1.067], 1.008 0.977–1.040]). Overall, 277, 216 201 identified UC. Total 733 classified tier 3 (found only one tissue) druggable targets, 57 2 tissues, 51 protein-coding genes) 9 three tissues). Among 60 over 2, 18 overlapped enriched mitochondria, antigen presentation, processing immune cell regulation Three (LRRK2, RAB29 HLA-DQA2) colocalization analysis. LRRK2 reported be genes, HLA-DQA2 first time potential This study established a reliable relationship, possible pathways which had important implications intervention treatment diseases simultaneously.

Language: Английский

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Brain-Gut Interplay: Cognitive Performance and Biomarker Correlations in IBD Patients

Journal of Clinical Medicine, Journal Year: 2025, Volume and Issue: 14(7), P. 2293 - 2293

Published: March 27, 2025

Background/Objectives: Inflammatory bowel diseases (IBD), including mainly ulcerative colitis (UC) and Crohn's disease (CD), have been associated with cognitive psychological changes, though the mechanisms remain unclear. Methods: This prospective case-control study aimed to evaluate performance biomarkers (homocysteine, serum amyloid A, brain-derived neurotrophic factor, S100B protein) in IBD patients. Results: A total of 90 individuals (34 UC, 21 CD, 35 controls) were assessed using Montreal Cognitive Assessment (MoCA), Memory Impairment Index (MIS), biomarker analysis. MoCA MIS testing showed significant differences between controls, lower scores observed groups (p = 0.003, p 0.015). Regarding trail-making tests, digit symbol substitution forward backward spans, no changes observed. No functional deficits daily activities. Biomarker analysis revealed factor higher levels patients, correlated MOCA scores. There distress patients controls. Subtle declines noted across all during 1-year follow-up, without any statistical significance when compared. Conclusions: In conclusion, reported compared while depression anxiety Higher BDNF better functioning, functioning.

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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The dual role of microglia in Alzheimer’s disease: from immune regulation to pathological progression

Frontiers in Aging Neuroscience, Journal Year: 2025, Volume and Issue: 17

Published: March 27, 2025

Alzheimer’s disease (AD) is a widespread neurodegenerative disorder and one of the major challenges for public health. Despite extensive research, role microglia in AD remains complex dual. The aim this review to summarize most recent advances research regarding dual concerning both immunomodulation pathological progression by considering mechanisms activation microglia, effects on Aβ clearance, tau pathology, impacts due genetic variations microglial functions. Among these findings are status M1 M2 phenotypes, crucial that variants like TREM2 have modulating response microglia. This describes how modulation signaling pathway might be exploited therapeutically treatment underlines relevance personalized medicine approach.

Language: Английский

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Gut Microbiota and Neuroinflammation: An Interconnected Nexus of Health and Neurodegenerative Disease

OBM Neurobiology, Journal Year: 2024, Volume and Issue: 08(04), P. 1 - 28

Published: Nov. 20, 2024

The gut microbiota, a complex ecosystem of billions microorganisms in the human digestive tract, plays crucial role maintaining health. Recent studies have highlighted bidirectional communication pathway called gut-brain axis between and brain. This is significantly influenced by microbiota its interactions with immune system, which can affect brain function contribute to inflammation. study aims provide comprehensive overview relationship neuroinflammation, focusing on underlying mechanisms implications for neurological disorders. A thorough literature review was conducted, examining impact this interaction, potential therapeutic applications. modulates neuroinflammation through various pathways, including producing short-chain fatty acids (SCFAs), modulating regulating nervous system. Dysbiosis, characterized an imbalance composition, has been associated increased risk conditions. Interventions such as probiotics, prebiotics, fecal transplantation show promise treating neuroinflammation. Understanding pivotal essential developing novel strategies prevent manage diseases. Further research needed elucidate involved, identify specific profiles different disorders, optimize personalized therapies based microbiome modulation.

Language: Английский

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