scholarly journals Lipopolysaccharide-binding protein (LBP) can reverse the amyloid state of fibrin seen or induced in Parkinson’s disease: implications for its aetiology

2017 ◽  
Author(s):  
Etheresia Pretorius ◽  
Sthembile Mbotwe ◽  
Douglas B. Kell
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Blood Clotting ◽  
Binding Protein ◽  
Treatment Strategies ◽  
Lipopolysaccharide Binding Protein ◽  
Novel Treatment ◽  
Novel Treatment Strategies ◽  
Lipopolysaccharide Binding ◽  
Scanning Electron

AbstractThe thrombin-induced polymerisation of fibrinogen to form fibrin is well established as a late stage of blood clotting. In recent work, we showed that the presence of tiny amounts of bacterial lipopolysaccharide (LPS) could cause these clots to adopt an amyloid form, that could be observed via scanning electron microscopy (SEM) or via the fluorescence of thioflavin-T. This could be prevented by the prior addition of lipopolysaccharide-binding protein (LBP). We had also observed by SEM this unusual clotting in the blood of patients with Parkinson’s disease (PD). We here show that this too can be prevented by LBP, thereby implicating such inflammatory microbial cell wall products in the aetiology of the disease. This may lead to novel treatment strategies in PD designed to target microbes and their products.

scholarly journals Intestinal Dysbiosis and Lowered Serum Lipopolysaccharide-Binding Protein in Parkinson’s Disease

PLoS ONE ◽  
2015 ◽  
Vol 10 (11) ◽  
pp. e0142164 ◽  
Author(s):  
Satoru Hasegawa ◽  
Sae Goto ◽  
Hirokazu Tsuji ◽  
Tatsuya Okuno ◽  
Takashi Asahara ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Binding Protein ◽  
Lipopolysaccharide Binding Protein ◽  
Intestinal Dysbiosis ◽  
Lipopolysaccharide Binding ◽  
Lowered Serum

scholarly journals Mitophagy in Parkinson’s Disease: From Pathogenesis to Treatment

Cells ◽  
2019 ◽  
Vol 8 (7) ◽  
pp. 712 ◽  
Author(s):  
Jia Liu ◽  
Weijin Liu ◽  
Ruolin Li ◽  
Hui Yang
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Treatment Strategies ◽  
Critical Component ◽  
Mitochondrial Quality Control ◽  
Therapeutic Implications ◽  
Novel Treatment ◽  
Mitochondrial Defects ◽  
Novel Treatment Strategies ◽  
Related Proteins

Parkinson’s disease (PD) is the second most common neurodegenerative disease. The pathogenesis of PD is complicated and remains obscure, but growing evidence suggests the involvement of mitochondrial and lysosomal dysfunction. Mitophagy, the process of removing damaged mitochondria, is compromised in PD patients and models, and was found to be associated with accelerated neurodegeneration. Several PD-related proteins are known to participate in the regulation of mitophagy, including PINK1 and Parkin. In addition, mutations in several PD-related genes are known to cause mitochondrial defects and neurotoxicity by disturbing mitophagy, indicating that mitophagy is a critical component of PD pathogenesis. Therefore, it is crucial to understand how these genes are involved in mitochondrial quality control or mitophagy regulation in the study of PD pathogenesis and the development of novel treatment strategies. In this review, we will discuss the critical roles of mitophagy in PD pathogenesis, highlighting the potential therapeutic implications of mitophagy regulation.

Plasma Lipopolysaccharide-Binding Protein Reflects Risk and Progression of Parkinson’s Disease

2021 ◽  
pp. 1-11
Author(s):  
Szu-Ju Chen ◽  
Yu-Chiao Chi ◽  
Chang-Han Ho ◽  
Wei-Shiung Yang ◽  
Chin-Hsien Lin
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mmse Score ◽  
Binding Protein ◽  
Motor Score ◽  
Lipopolysaccharide Binding Protein ◽  
Cox Regression Analysis ◽  
Updrs Part ◽  
Lipopolysaccharide Binding

Background: Lipopolysaccharide-binding protein (LBP) presents bacterial endotoxin, lipopolysaccharides, to cellular surface pattern receptors for immune responses in the gut-brain axis of Parkinson’s disease (PD). Objective: We investigated whether plasma LBP levels were associated with PD severity and progression. Methods: This study included 397 participants (248 PD patients and 149 controls). We measured participants’ plasma levels of LBP and pro-inflammatory cytokines, including TNF-α, IL-6, andIL-17A. PD patients underwent motor and cognition evaluations at baseline and at a mean follow-up interval of 4.7±2.3 years. We assessed the progression of motor and cognition symptoms based on changes in the Movement Disorder Society-Unified Parkinson’s Disease Rating Scale (MDS-UPDRS) part III motor score and Mini-Mental State Examination (MMSE) score, respectively. Results: Plasma LBP levels were lower in PD patients than controls (9.08±2.91 vs. 10.10±3.00μg/ml, p <  0.01). A multiple logistic regression model with adjustment for age, sex, and plasma cytokine levels revealed that reduced plasma LBP levels were associated with increased PD risk (odds ratio 0.816, [95% CI 0.717–0.929], p = 0.002). Among PD patients, LBP levels were correlated with MDS-UPDRS part III motor score after adjustment for confounders (coefficient = 0.636, p = 0.017), but not with MMSE score. Adjusted Cox regression analysis showed that higher plasma LBP levels associated with faster motor progression (adjusted hazard ratio 1.084 [95% CI 1.011–1.163], p = 0.024) during follow-up. Conclusion: Our results demonstrated that plasma LBP levels reflect risk, motor symptom severity and progression in patients with PD.

scholarly journals Urinary proteome profiling for stratifying patients with familial Parkinson’s disease

2020 ◽  
Author(s):  
Sebastian Virreira Winter ◽  
Ozge Karayel ◽  
Maximilian T Strauss ◽  
Shalini Padmanabhan ◽  
Matthew Surface ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Biomarker Discovery ◽  
Treatment Strategies ◽  
Disease Manifestation ◽  
Proteome Profiling ◽  
Urinary Proteome ◽  
G2019s Mutation ◽  
Associated Proteins ◽  
Novel Treatment Strategies

SUMMARYThe prevalence of Parkinson’s disease (PD) is increasing but the development of novel treatment strategies and therapeutics altering the course of the disease would benefit from specific, sensitive and non-invasive biomarkers to detect PD early. Here, we describe a scalable and sensitive mass spectrometry (MS)-based proteomic workflow for urinary proteome profiling. Our workflow enabled the reproducible quantification of more than 2,000 proteins in more than 200 urine samples using minimal volumes from two independent patient cohorts. The urinary proteome was significantly different between PD patients and healthy controls, as well as between LRRK2 G2019S carriers and non-carriers in both cohorts. Interestingly, our data revealed lysosomal dysregulation in individuals with the LRRK2 G2019S mutation. When combined with machine learning, the urinary proteome data alone was sufficient to classify mutation status and disease manifestation in mutation carriers remarkably well, identifying VGF, ENPEP and other PD-associated proteins as the most discriminating features. Taken together, our results validate urinary proteomics as a valuable strategy for biomarker discovery and patient stratification in PD.

scholarly journals Mitochondrial Contribution to Parkinson's Disease Pathogenesis

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Anthony H. V. Schapira ◽  
Matthew Gegg
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Treatment Strategies ◽  
Gene Mutations ◽  
Alpha Synuclein ◽  
Genetic Causes ◽  
Novel Treatment Strategies ◽  
Synuclein Proteins ◽  
And Oxidative Stress

The identification of the etiologies and pathogenesis of Parkinson's disease (PD) should play an important role in enabling the development of novel treatment strategies to prevent or slow the progression of the disease. The last few years have seen enormous progress in this respect. Abnormalities of mitochondrial function and increased free radical mediated damage were described in post mortem PD brain before the first gene mutations causing familial PD were published. Several genetic causes are now known to induce loss of dopaminergic cells and parkinsonism, and study of the mechanisms by which these mutations produce this effect has provided important insights into the pathogenesis of PD and confirmed mitochondrial dysfunction and oxidative stress pathways as central to PD pathogenesis. Abnormalities of protein metabolism including protein mis-folding and aggregation are also crucial to the pathology of PD. Genetic causes of PD have specifically highlighted the importance of mitochondrial dysfunction to PD: PINK1, parkin, DJ-1 and most recently alpha-synuclein proteins have been shown to localise to mitochondria and influence function. The turnover of mitochondria by autophagy (mitophagy) has also become a focus of attention. This review summarises recent discoveries in the contribution of mitochondrial abnormalities to PD etiology and pathogenesis.

scholarly journals Higher Lipopolysaccharide Binding Protein and Chemerin Concentrations Were Associated with Metabolic Syndrome Features in Pediatric Subjects with Abdominal Obesity during a Lifestyle Intervention

Nutrients ◽  
2021 ◽  
Vol 13 (2) ◽  
pp. 289
Author(s):  
Amelia Marti ◽  
Isabel Martínez ◽  
Ana Ojeda-Rodríguez ◽  
María Cristina Azcona-Sanjulian
Keyword(s):  
Metabolic Syndrome ◽  
Children And Adolescents ◽  
Lifestyle Intervention ◽  
Abdominal Obesity ◽  
Plasma Levels ◽  
Intervention Program ◽  
Binding Protein ◽  
Controlled Trial ◽  
Lipopolysaccharide Binding Protein ◽  
Lipopolysaccharide Binding

Background: Elevated circulating plasma levels of both lipopolysaccharide-binding protein (LBP) and chemerin are reported in patients with obesity, but few studies are available on lifestyle intervention programs. We investigated the association of both LBP and chemerin plasma levels with metabolic syndrome (MetS) outcomes in a lifestyle intervention in children and adolescents with abdominal obesity Methods: Twenty-nine patients enrolled in a randomized controlled trial were selected. The lifestyle intervention with a 2-month intensive phase and a subsequent 10-month follow-up consisted of a moderate calorie-restricted diet, recommendations to increase physical activity levels, and nutritional education. Results: Weight loss was accompanied by a significant reduction in MetS prevalence (−43%; p = 0.009). Chemerin (p = 0.029) and LBP (p = 0.033) plasma levels were significantly reduced at 2 months and 12 months, respectively. At the end of intervention, MetS components were associated with both LBP (p = 0.017) and chemerin (p < 0.001) plasma levels. Conclusions: We describe for the first time a reduction in both LBP and chemerin plasma levels and its association with MetS risk factors after a lifestyle intervention program in children and adolescents with abdominal obesity. Therefore, LBP and chemerin plasma levels could be used as biomarkers for the progression of cardiovascular risk in pediatric populations.

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