scholarly journals Clearing Extracellular Alpha-Synuclein from Cerebrospinal Fluid: A New Therapeutic Strategy in Parkinson’s Disease

2018 ◽  
Vol 8 (4) ◽  
pp. 52 ◽  
Author(s):  
Manuel Menéndez-González ◽  
Huber Padilla-Zambrano ◽  
Cristina Tomás-Zapico ◽  
Benjamin García
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Therapeutic Strategy ◽  
Alpha Synuclein

scholarly journals Alpha-Synuclein Protofibrils in Cerebrospinal Fluid: A Potential Biomarker for Parkinson's Disease

2020 ◽  
Vol 10 (4) ◽  
pp. 1429-1442
Author(s):  
Marianne von Euler Chelpin ◽  
Linda Söderberg ◽  
Johanna Fälting ◽  
Christer Möller ◽  
Marco Giorgetti ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Single Molecule ◽  
Area Under The Curve ◽  
Corticobasal Degeneration ◽  
Alpha Synuclein ◽  
Cross Reactivity ◽  
Potential Biomarker ◽  
Csf Levels

Background: Currently, there is no established biomarker for Parkinson's disease (PD) and easily accessible biomarkers are crucial for developing disease-modifying treatments. Objective: To develop a novel method to quantify cerebrospinal fluid (CSF) levels of α-synuclein protofibrils (α-syn PF) and apply it to clinical cohorts of patients with PD and atypical parkinsonian disorders. Methods: A cohort composed of 49 patients with PD, 12 with corticobasal degeneration (CBD), 22 with progressive supranuclear palsy, and 33 controls, that visited the memory clinic but had no biomarker signs of Alzheimer’s disease (AD, tau<350 pg/mL, amyloid-beta 42 (Aβ42)>530 pg/mL, and phosphorylated tau (p-tau)<60 pg/mL) was used in this study. The CSF samples were analyzed with the Single molecule array (Simoa) technology. Total α-synuclein (α-syn) levels were analyzed with a commercial ELISA-kit. Results: The assay is specific to α-syn PF, with no cross-reactivity to monomeric α-syn, or the β- and γ-synuclein variants. CSF α-syn PF levels were increased in PD compared with controls (62.1 and 40.4 pg/mL, respectively, p = 0.03), and CBD (62.1 and 34.2 pg/mL, respectively, p = 0.02). The accuracy of predicting PD using α-syn PF is significantly different from controls (area under the curve 0.68, p = 0.0097) with a sensitivity of 62.8% and specificity of 67.7%. Levels of total α-syn were significantly different between the PD and CBD groups (p = 0.04). Conclusion: The developed method specifically quantifies α-syn PF in human CSF with increased concentrations in PD, but with an overlap with asymptomatic elderly controls.

scholarly journals Different structures and pathologies of alpha-synuclein fibrils derived from preclinical and postmortem patients of Parkinson's disease

2021 ◽  
Author(s):  
Yun Fan ◽  
Yunpeng Sun ◽  
Wenbo Yu ◽  
Youqi Tao ◽  
Wencheng Xia ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Lewy Bodies ◽  
Alpha Synuclein ◽  
Electron Microscopic ◽  
Lewy Neurites ◽  
The Difference ◽  
A Minor

alpha-Synuclein (alpha-syn) fibrillar aggregates are the major component of Lewy bodies and Lewy neurites presenting as the pathology hallmark of Parkinson's disease (PD). Studies have shown that alpha-syn is potential to form different conformational fibrils associated with different synucleinopathies, but whether the conformation of alpha-syn fibrils changes in different phases of related diseases is to be explored. Here, we amplified alpha-syn aggregates from the cerebrospinal fluid (CSF) of preclinical (pre-PD) and late-stage postmortem PD (post-PD) patients. Our results show that compared to the CSF of pre-PD, that of post-PD is markedly stronger in seeding in vitro alpha-syn aggregation, and the amplified fibrils are more potent in inducing endogenous alpha-syn aggregation in neurons. Cryo-electron microscopic structures further reveal that the difference between the pre-PD- and post-PD-derived fibrils lies on a minor polymorph which in the pre-PD fibrils is morphologically straight, while in the post-PD fibrils represents a single protofilament assembled by a distinctive conformation of alpha-syn. Our work demonstrates structural and pathological differences between pre-PD and post-PD alpha-syn aggregation and suggests potential alteration of alpha-syn fibrils during the progression of PD clinical phases.

scholarly journals Cerebrospinal fluid lysosomal enzymes and alpha‐synuclein in Parkinson's disease

2014 ◽  
Vol 29 (8) ◽  
pp. 1019-1027 ◽  
Author(s):  
Lucilla Parnetti ◽  
Davide Chiasserini ◽  
Emanuele Persichetti ◽  
Paolo Eusebi ◽  
Shiji Varghese ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Cerebrospinal Fluid ◽  
Lysosomal Enzymes ◽  
Alpha Synuclein

scholarly journals Dietary Macronutrient Management to Treat Mitochondrial Dysfunction in Parkinson’s Disease

2019 ◽  
Vol 20 (8) ◽  
pp. 1850 ◽  
Author(s):  
Rijan Bajracharya ◽  
Neil A. Youngson ◽  
J. William O. Ballard
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Dysfunction ◽  
Mitochondrial Function ◽  
Therapeutic Strategy ◽  
Management Strategies ◽  
Alpha Synuclein ◽  
Mitochondrial Energy Metabolism ◽  
Low Protein ◽  
Drosophila Model

Mitochondrial dysfunction has been demonstrated to play an important role in the pathogenesis of Parkinson’s disease (PD). The products of several PD-associated genes, including alpha-synuclein, parkin, pink1, protein deglycase DJ-1, and leucine rich repeat kinase 2, have important roles in mitochondrial biology. Thus, modifying mitochondrial function could be a potential therapeutic strategy for PD. Dietary management can alter mitochondrial function as shifts in dietary macronutrients and their ratios in food can alter mitochondrial energy metabolism, morphology and dynamics. Our studies have established that a low protein to carbohydrate (P:C) ratio can increase lifespan, motor ability and mitochondrial function in a parkin mutant Drosophila model of PD. In this review, we describe mitochondrial dysfunction in PD patients and models, and dietary macronutrient management strategies to reverse it. We focus on the effects of protein, carbohydrate, fatty acids, and their dietary ratios. In addition, we propose potential mechanisms that can improve mitochondrial function and thus reverse or delay the onset of PD.

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