Association of metabolic syndrome and its components with Parkinson’s disease: a cross-sectional study

BMC Endocrine Disorders, Год журнала: 2024, Номер 24(1)

Опубликована: Июнь 19, 2024

Abstract Background The interrelation between metabolic syndrome (MetS) and Parkinson’s disease (PD) likely arises from shared pathological mechanisms. This study thus aims to examine the impact of MetS its components on PD. Methods utilized data extracted National Health Nutrition Examination Survey database spanning 1999 2020. random forest algorithm was applied fill in missing data. Propensity score optimal full matching conducted. were adjusted by total weights derived both sampling weights. weighted create multifactor logistic regression models. Odds ratios (ORs) average marginal effects, along with their corresponding 95% confidence intervals (CIs), calculated. Results did not significantly affect risk PD (OR: 1.01; CI: 0.77, 1.34; P = 0.92). Hypertension elevated 1.33; 1.01, 1.76; 0.045), accompanied a 0.26% increased probability occurrence (95% 0.01%, 0.52%; 0.04). Diabetes mellitus (DM) had 1.38 times greater likelihood developing (OR:1.38; 1.004, 1.89; 0.046), 0.32% -0.03%, 0.67%; 0.07). Nevertheless, no correlation observed hyperlipidemia, waist circumference Conclusion does PD; however, hypertension DM increase

Язык: Английский

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A retrospective study of the MDS criteria for prodromal Parkinson’s disease in the general population

npj Parkinson s Disease, Год журнала: 2024, Номер 10(1)

Опубликована: Июнь 26, 2024

Abstract The Movement Disorder Society developed research criteria for the detection of prodromal phase Parkinson’s disease (PD). Accurate identification this is essential early interventions. Therefore, we investigated diagnostic value these in general population. Lifelines an ongoing cohort study 167,000 participants from population Northern Netherlands. 160 self-reported to have PD during three rounds follow-up five years each. Data were available infer six out eleven risk markers, and twelve markers. We retrospectively compared stage a group ‘converters’ with 320 age- sex-matched controls. overall incidence rate was 0.20 per 1.000 person-years (95% CI: 0.049−0.36), increasing age rates higher men. median probability PD-converters 1.29% (interquartile range: 0.46−2.9), 0.83% (0.39−1.8) controls ( P = 0.014). MDS set had ROC-AUC 0.577, therefore not sufficient adequately predict conversion PD. unable using selection criteria. Ancillary investigations are required improve accuracy criteria, but most precluded large-scale use. Strategies, including olfactory tests or alpha-synuclein seeding amplification assays may

Язык: Английский

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The neuroprotective effect of vitamin D in Parkinson's disease: association or causation

Nutritional Neuroscience, Год журнала: 2023, Номер 27(8), С. 870 - 886

Опубликована: Сен. 20, 2023

ABSTRACTParkinson's disease (PD) is a chronic neurodegenerative (NDD) due to the degeneration of dopaminergic neurons (DNs) in substantia nigra (SN). PD characterized by diverse motor symptoms such as rigidity, resting tremors, and bradykinesia, non-motor cognitive dysfunction sleep disturbances. Vitamin D (VD), VD receptor (VDR), metabolites are present brain play role maintaining development, differentiation, functions DNs. VDRs exert protective effects against neuropathology modulating functional capacity DNs neurotransmission SN. In virtue its anti-inflammatory antioxidant activities, could be effective prevention treatment PD. exerts neuroprotective effect reducing oxidative stress mitochondrial dysfunction, increasing autophagy brain-derived neurotrophic factor (BDNF). Low serum level connected with development dementia The VD-mediated augmenting interrelated safeguarding synaptic plasticity modulation neurotransmitter release. deficiency linked severity olfactory which precedes progression symptomatic However, precise remains unidentified, there conflict about whether can ameliorate or not.KEYWORDS: Parkinson's diseaseVitamin DVD receptorBDNFsubstantia nigraAutophagyOxidative stressdopaminergic AcknowledgementsNot applicable.Authors' contributionsAAH conceptualized manuscript, wrote, edited, reviewed main text approved final edition manuscript.Disclosure statementNo potential interest was reported author(s).Additional informationFundingThe author(s) no funding associated work featured this article.

Язык: Английский

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Integrated network pharmacology and phosphoproteomic analyses of Baichanting in Parkinson's disease model mice

Heliyon, Год журнала: 2024, Номер 10(6), С. e26916 - e26916

Опубликована: Фев. 27, 2024

The incidence rate of Parkinson's disease (PD) is increasing yearly. Neuronal apoptosis caused by abnormal protein phosphorylation closely related to the pathogenesis disease. At present, few PD-specific pathways have been revealed. To investigate effect Baichanting (BCT) on from perspective phosphorylation, α-syn transgenic mice were selected observe behavioral changes mice, and substantia nigra cells detected HE method TUNEL method. Network pharmacology combined with proteomics was used find relevant targets for BCT treatment PD further verified PRM western blotting. improved morphology neurons in reduced neuronal apoptosis. main enriched network results apoptosis, p53 signaling pathway autophagy. Western blot showed that significantly regulated expression levels BAX, Caspase-3, LC3B, P53 mTOR upregulated autophagy alleviate Using phosphorylated validation, we found Pak5, Grin2b, Scn1a, BcaN, L1cam Braf are correlated web-based pharmacological screen may be involved p53/mTOR-mediated pathways. can inhibit activation p53/mTOR pathway, thereby enhancing function cells, reducing which mechanism its neuroprotective effect.

Язык: Английский

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The diagnostic value of neutrophil to lymphocyte ratio, albumin to fibrinogen ratio, and lymphocyte to monocyte ratio in Parkinson’s disease: a retrospective study

Frontiers in Neurology, Год журнала: 2024, Номер 15

Опубликована: Сен. 2, 2024

Background Parkinson’s disease (PD) is a prevalent disorder of the central nervous system, marked by degeneration dopamine (DA) neurons in ventral midbrain. In pathogenesis PD, inflammation hypothesis has been concerned. This study aims to investigate clinical indicators peripheral PD patients and explore diagnostic value neutrophil-to-lymphocyte ratio (NLR), albumin-to-fibrinogen (AFR), lymphocyte-to-monocyte (LMR) assessing risk. Methods included 186 with 201 matched healthy controls (HC) baseline data. Firstly, differences hematological between group participants were compared analyzed. Univariate multivariate regression analyses then conducted. Smooth curve fitting was applied further validate relationships NLR, LMR, AFR, PD. Subsequently, subgroup analysis conducted according different duration Hoehn Yahr (H&Y) stage, comparing indicators. Finally, receiver operating characteristic (ROC) employed assess AFR Results Compared HC group, showed significantly higher levels hypertension, diabetes, neutrophil count, monocyte CRP, homocysteine, fibrinogen, NLR. Conversely, lymphocyte HDL, LDL, TG, TC, uric acid, albumin lower. The model indicated that NLR (OR = 1.79, 95% CI: 1.39–2.31, p < 0.001), LMR 0.75, 0.66–0.85, 0.79, 0.73–0.85, 0.001) significant factors associated revealed positively linked risk, whereas inversely it. ROC analysis, AUC 0.7290, sensitivity 63.98%, specificity 76.00%. 0.6200, 50.54%, 71.50%. 0.6253, 48.39%, 73.00%. combination 0.7498, 74.19%, 64.00%. Conclusion Our findings indicate are may serve as markers.

Язык: Английский

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Identifying MSMO1, ELOVL6, AACS, and CERS2 related to lipid metabolism as biomarkers of Parkinson's disease

Research Square (Research Square), Год журнала: 2024, Номер unknown

Опубликована: Апрель 23, 2024

Abstract The mechanisms underlying lipid metabolic disorders in Parkinson's diseases (PD) remain unclear. Weighted Gene Co-Expression Network Analysis (WGCNA) was conducted to identify PD-related modular genes and differentially expressed (DEGs). Lipid metabolism-related (LMRGs) were extracted from Molecular Signatures Database. Candidate assessed with overlapping genes, DEGs, LMRGs for the purpose of building protein-protein interaction(PPI) networks. Then, biomarkers generated by machine learning Backpropagation Neural development according candidate genes. Biomarker-based enrichment network modulation analyses executed investigate related signal pathway. Following dimensionality reduction clustering annotation, scRNA-seq submitted cellular interactions trajectory analysis analyze regulatory critical cells. Finally, qRT-PCR confirm expression PD patients. Four (MSMO1, ELOVL6, AACS, CERS2) obtained highly predictive after mentioned above. OPC, Oli, Neu cells primary sites studies. we confirmed mRNA MSMO1, ELOVL6 AACS downregulated patients comparing control, while CERS2 upregulated. In conclusion, could be new diagnosing treating PD.

Язык: Английский

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Quantitative Determination of a Series of Oxysterols by an Optimized LC-MS/MS Analysis in Different Tissue Types

International Journal of Molecular Sciences, Год журнала: 2024, Номер 26(1), С. 77 - 77

Опубликована: Дек. 25, 2024

Oxysterols, as metabolites of cholesterol, play a key role in cholesterol homeostasis, autophagosome formation, and regulation immune responses. Disorders oxysterol metabolism are closely related to the pathogenesis neurodegenerative diseases. To systematically investigate profound molecular regulatory mechanisms diseases, it is necessary quantify oxysterols their central peripheral biospecimens simultaneously accurately. However, there lot unsolved problems with existing methods, such hindrance applying single method different biological specimens or challenge simultaneous quantification due differential groups on ends side chains. Herein, according physicochemical properties structure oxysterols, an optimized liquid chromatography-tandem mass spectrometry for was established by optimizing sample preparation process, chromatographic conditions, mobile phase pH, solvent selection. Seven were detected this method, including 27-hydroxycholesterol, 7α-hydroxycholesterol, 7α,27-dihydroxycholesterol, 7-dehydrocholesterol, 7α-hydroxy-3-oxo-4-cholestenoic acid, 3-hydroxy-5-cholestenoic 24(S)-hydroxycholesterol. Non-derivatization extraction methyl tert-butyl ether used biospecimens, followed separation phenyl hexyl column. By repeated validation, exhibited satisfactory linearity, precision, recovery, sensitivity, repeatability, stability, successfully applied detection plasma, cerebral cortex, liver mouse. In summary, our enables concurrent analysis various presenting broad range applicability.

Язык: Английский

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p75NTR modulation by LM11A-31 counteracts oxidative stress and cholesterol dysmetabolism in a rotenone-induced cell model of Parkinson’s disease

bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Дек. 25, 2024

Abstract Neurotrophins play pivotal roles in the development and proper functioning of nervous system. The effects these growth factors are mediated through binding high-affinity receptors, known as Trks, well low-affinity receptor p75NTR. latter has capacity to induce complex signal pathways, it favors both pro-survival pro-apoptotic cascades depending on physiopathological condition. Recent findings have indicated that p75NTR expression is increased post-mortem Parkinson’s disease (PD) brains, this upregulation associated with a significant reduction neuroprotection. Given its double-edged sword nature, recently been identified promising therapeutic target counteract neurodegenerative events. present study aims assess neuroprotective modulation rotenone-induced neuronal model PD. To end, differentiated SH-SY5Y cells were exposed rotenone mimic PD phenotype, small molecule LM11A-31 was used modulate activity. main results revealed significantly mitigated hallmarks PD, including cell death, neuromorphological aberrations, α-synuclein accumulation. Pharmacological manipulation also reduced oxidative damage by increasing transcriptional regulate antioxidant response decreasing pro-oxidant NADPH-oxidase modulatory subunits. Furthermore, hampered cholesterol buildup induced rotenone, normalizing proteins involved biosynthesis, uptake intracellular trafficking. Taken together, suggest may represent novel approach counteracting abnormalities redox metabolism.

Язык: Английский

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