Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity

Wang, Peng; Li, Xin; Li, Xuran; Yang, Weiwei; Yu, Shun

doi:10.1155/2016/7596482

Cited by 11 publications

(9 citation statements)

References 43 publications

(51 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…e ELISA assay used for measuring pS-α-syn-RBC was established previously [25] and has been applied to detect pS-α-syn in aging monkey brains [24][25][26] and pS-α-syn formed in PD plasma [27]. e detection antibody was 3D5 mouse monoclonal anti-α-syn, which recognizes a sequence of 115-121 amino acids specific to human α-syn [23] and has been demonstrated previously for its specificity in detecting α-syn in human RBCs [16].…”

Section: Discussionmentioning

confidence: 99%

Phosphorylated Alpha-Synuclein in Red Blood Cells as a Potential Diagnostic Biomarker for Multiple System Atrophy: A Pilot Study

Yang

et al. 2020

Parkinson's Disease

Self Cite

View full text Add to dashboard Cite

Diagnosis of multiple system atrophy (MSA) remains a challenge, due to the complexity and overlapping of its symptoms with other Parkinsonian disorders. e critical role of alpha-synuclein (α-syn) in the pathogenesis of MSA makes it an ideal biomarker for the diagnosis of MSA. Although α-syn alterations in cerebrospinal fluid (CSF) and blood plasma have been extensively assessed for the utility in diagnosing MSA, inconsistent results have been obtained, presumably due to the contamination by hemolysis and other confounding factors. In this study, levels of serine 129-phosphorylated α-syn (pS-α-syn), a major pathologic form of α-syn, in red blood cells (RBCs), were measured using ELISA in a Chinese cohort consisting of 107 MSA patients and 220 healthy controls. A significant increase in the levels of pS-α-syn in RBCs (pS-α-syn-RBC) was observed in MSA patients than in healthy controls (14.02 ± 4.02 ng/mg versus 11.89 ± 3.57 ng/mg; p < 0.0001). Receiver operating characteristic curve (ROC) indicated that pS-α-syn-RBC discriminated the patients well from the controls with a sensitivity of 80.37% (95% confidence interval (CI): 71.58%-87.42%), a specificity of 88.64% (95% CI: 83.68%-92.51%), and an area under the curve (AUC) of 0.91 (95% CI: 0.87-0.94). e levels of pS-α-syn-RBC were negatively correlated with RBD-HK scores and differed between MSA-P and MSA-C subtypes (13.27 ± 1.91 versus 12.19 ± 3.04; p � 0.025). e difference between subtypes was seen at Hoehn and Yahr stages 3 and 4, and the age at onset (AAO) between 60 and 69 years (p � 0.016). e results suggest that pS-α-syn-RBC is increased in MSA patients and can be used as a potential diagnostic biomarker for MSA.

show abstract

Section: Discussionmentioning

confidence: 99%

Phosphorylated Alpha-Synuclein in Red Blood Cells as a Potential Diagnostic Biomarker for Multiple System Atrophy: A Pilot Study

Yang

et al. 2020

Parkinson's Disease

Self Cite

View full text Add to dashboard Cite

show abstract

“…The ELISA assay used for measuring pS-α-syn-RBC levels was established previously and has been applied to detect pS-α-syn in monkey brains (Liu et al, 2015 ) and pS-α-syn formed in PD plasma (Wang et al, 2016 ). The detection antibody was 3D5 mouse monoclonal anti-α-syn, which recognizes a sequence of 115–121 amino acids specific to human α-syn (Yu et al, 2007 ) and has been well-characterized previously for its specificity in detecting α-syn in human RBCs (Wang et al, 2015 ).…”

Section: Discussionmentioning

confidence: 99%

Alterations of Erythrocytic Phosphorylated Alpha-Synuclein in Different Subtypes and Stages of Parkinson's Disease

et al. 2021

Front. Aging Neurosci.

Self Cite

View full text Add to dashboard Cite

Serine 129-phosphorylated alpha-synuclein (pS-α-syn) is a major form of α-syn relevant to the pathogenesis of Parkinson's disease (PD), which has been recently detected in red blood cells (RBCs). However, alterations of RBC-derived pS-α-syn (pS-α-syn-RBC) in different subtypes and stages of PD remains to be investigated. In the present study, by using enzyme-linked immunosorbent assay (ELISA) to measure pS-α-syn-RBC, we demonstrated significantly higher levels of pS-α-syn-RBC in PD patients than in healthy controls. pS-α-syn-RBC separated the patients well from the controls, with a sensitivity of 93.39% (95% CI: 90.17–95.81%), a specificity of 93.11% (95% CI: 89.85–95.58%), and an area under the curve (AUC) of 0.96. Considering motor subtypes, the levels of pS-α-syn-RBC were significantly higher in late-onset than young-onset PD (p = 0.013) and in those with postural instability and gait difficulty than with tremor-dominant (TD) phenotype (p = 0.029). In addition, the levels of pS-α-syn-RBC were also different in non-motor subtypes, which were significantly lower in patients with cognitive impairment (p = 0.012) and olfactory loss (p = 0.004) than in those without such symptoms. Moreover, the levels of pS-α-syn-RBC in PD patients were positively correlated with disease duration and Hoehn & Yahr stages (H&Y) (p for trend =0.02 and <0.001) as well as UPDRS III (R2 = 0.031, p = 0.0042) and MoCA scores (R2 = 0.048, p = 0.0004). The results obtained suggest that pS-α-syn-RBC can be used as a potential biomarker for not only separating PD patients from healthy controls but also predicting the subtypes and stages of PD.

show abstract

“…Porcine choroid plexus produces several neurotrophins and can be safely delivered to the striatum in an encapsulated formulation to protect them from immune attack [ 63 ]. NTCELL is an alginate-coated capsule containing clusters of neonatal porcine choroid plexus cells [ 64 ]. In 2013, Living Cell technologies hosted a phase I/II trial of NTCELL implantation ( Table 2 ).…”

Section: Pd Therapeutic Strategies In Clinical Trialsmentioning

confidence: 99%

Current Therapies in Clinical Trials of Parkinson’s Disease: A 2021 Update

Prasad

Hung

2021

Pharmaceuticals

View full text Add to dashboard Cite

Parkinson’s disease (PD) is a progressive neurodegenerative disorder that currently has no cure, but treatments are available to improve PD symptoms and maintain quality of life. In 2020, about 10 million people worldwide were living with PD. In 1970, the United States Food and Drug Administration approved the drug levodopa as a dopamine replacement to manage PD motor symptoms; levodopa-carbidopa combination became commercialized in 1975. After over 50 years of use, levodopa is still the gold standard for PD treatment. Unfortunately, levodopa therapy-induced dyskinesia and OFF symptoms remain unresolved. Therefore, we urgently need to analyze each current clinical trial’s status and therapeutic strategy to discover new therapeutic approaches for PD treatment. We surveyed 293 registered clinical trials on ClinicalTrials.gov from 2008 to 16 June 2021. After excluded levodopa/carbidopa derivative add-on therapies, we identified 47 trials as PD treatment drugs or therapies. Among them, 19 trials are in phase I (41%), 25 trials are in phase II (53%), and 3 trials are in phase III (6%). The three phase-III trials use embryonic dopamine cell implant, 5-HT1A receptor agonist (sarizotan), and adenosine A2A receptor antagonist (caffeine). The therapeutic strategy of each trial shows 29, 5, 1, 5, 5, and 2 trials use small molecules, monoclonal antibodies, plasma therapy, cell therapy, gene therapy, and herbal extract, respectively. Additionally, we discuss the most potent drug or therapy among these trials. By systematically updating the current trial status and analyzing the therapeutic strategies, we hope this review can provide new ideas and insights for PD therapy development.

show abstract

Blood Plasma of Patients with Parkinson’s Disease Increases Alpha-Synuclein Aggregation and Neurotoxicity

Cited by 11 publications

References 43 publications

Phosphorylated Alpha-Synuclein in Red Blood Cells as a Potential Diagnostic Biomarker for Multiple System Atrophy: A Pilot Study

Phosphorylated Alpha-Synuclein in Red Blood Cells as a Potential Diagnostic Biomarker for Multiple System Atrophy: A Pilot Study

Alterations of Erythrocytic Phosphorylated Alpha-Synuclein in Different Subtypes and Stages of Parkinson's Disease

Current Therapies in Clinical Trials of Parkinson’s Disease: A 2021 Update

Contact Info

Product

Resources

About