scholarly journals Verification of a Parkinson’s Disease Protein Signature in T-Lymphocytes by Multiple Reaction Monitoring

2014 ◽  
Vol 13 (8) ◽  
pp. 3554-3561 ◽  
Author(s):  
Tiziana Alberio ◽  
Kelly McMahon ◽  
Manuela Cuccurullo ◽  
Lee A. Gethings ◽  
Craig Lawless ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
T Lymphocytes ◽  
Multiple Reaction Monitoring ◽  
Reaction Monitoring ◽  
Disease Protein ◽  
Protein Signature

scholarly journals Neuroinflammation and protein pathology in Parkinson’s disease dementia

2020 ◽  
Vol 8 (1) ◽  
Author(s):  
Antonina Kouli ◽  
Marta Camacho ◽  
Kieren Allinson ◽  
Caroline H. Williams-Gray
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
T Lymphocytes ◽  
Substantia Nigra ◽  
Amyloid Β ◽  
Brain Regions ◽  
Parkinson’S Disease Dementia ◽  
Activated Microglia ◽  
Cell Counts ◽  
The Brain

AbstractParkinson’s disease dementia is neuropathologically characterized by aggregates of α-synuclein (Lewy bodies) in limbic and neocortical areas of the brain with additional involvement of Alzheimer’s disease-type pathology. Whilst immune activation is well-described in Parkinson’s disease (PD), how it links to protein aggregation and its role in PD dementia has not been explored. We hypothesized that neuroinflammatory processes are a critical contributor to the pathology of PDD. To address this hypothesis, we examined 7 brain regions at postmortem from 17 PD patients with no dementia (PDND), 11 patients with PD dementia (PDD), and 14 age and sex-matched neurologically healthy controls. Digital quantification after immunohistochemical staining showed a significant increase in the severity of α-synuclein pathology in the hippocampus, entorhinal and occipitotemporal cortex of PDD compared to PDND cases. In contrast, there was no difference in either tau or amyloid-β pathology between the groups in any of the examined regions. Importantly, we found an increase in activated microglia in the amygdala of demented PD brains compared to controls which correlated significantly with the extent of α-synuclein pathology in this region. Significant infiltration of CD4+ T lymphocytes into the brain parenchyma was commonly observed in PDND and PDD cases compared to controls, in both the substantia nigra and the amygdala. Amongst PDND/PDD cases, CD4+ T cell counts in the amygdala correlated with activated microglia, α-synuclein and tau pathology. Upregulation of the pro-inflammatory cytokine interleukin 1β was also evident in the substantia nigra as well as the frontal cortex in PDND/PDD versus controls with a concomitant upregulation in Toll-like receptor 4 (TLR4) in these regions, as well as the amygdala. The evidence presented in this study show an increased immune response in limbic and cortical brain regions, including increased microglial activation, infiltration of T lymphocytes, upregulation of pro-inflammatory cytokines and TLR gene expression, which has not been previously reported in the postmortem PDD brain.

scholarly journals The Parkinson's disease protein DJ-1 is neuroprotective due to cysteine-sulfinic acid-driven mitochondrial localization

2004 ◽  
Vol 101 (24) ◽  
pp. 9103-9108 ◽  
Author(s):  
Rosa M. Canet-Avilés ◽  
Mark A. Wilson ◽  
David W. Miller ◽  
Rili Ahmad ◽  
Chris McLendon ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Mitochondrial Localization ◽  
Sulfinic Acid ◽  
Cysteine Sulfinic Acid ◽  
Disease Protein

scholarly journals High glucose upregulation of early-onset Parkinson's disease protein DJ-1 integrates the PRAS40/TORC1 axis to mesangial cell hypertrophy

2011 ◽  
Vol 23 (8) ◽  
pp. 1311-1319 ◽  
Author(s):  
Falguni Das ◽  
Nirmalya Dey ◽  
Balachandar Venkatesan ◽  
Balakuntalam S. Kasinath ◽  
Nandini Ghosh-Choudhury ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
High Glucose ◽  
Early Onset ◽  
Mesangial Cell ◽  
Cell Hypertrophy ◽  
Disease Protein ◽  
Early Onset Parkinson’S Disease

scholarly journals Analysis on the Susceptibility Genes in Two Chinese Pedigrees with Familial Parkinson's Disease

2010 ◽  
Vol 2010 ◽  
pp. 1-4
Author(s):  
Changshui Xu ◽  
Jun Xu ◽  
Yanmin Zhang ◽  
Jianjun Ma ◽  
Hideshi Kawakami ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Susceptibility Genes ◽  
Alpha Synuclein ◽  
Missense Mutations ◽  
Chain Reaction ◽  
Disease Protein ◽  
Polymerase Chain ◽  
Familial Parkinson’S Disease ◽  
Exon 10

Objective. To screen the susceptibility genes in Chinese pedigrees with early-onset familial Parkinson's disease (FPD).Methods. Fifty-one genomic DNA samples extracted from two Chinese pedigrees with FPD, the alpha-synuclein genes (SNCA), the leucine-rich repeat kinase 2(LRRK2), PINK1(PTEN-induced putative kinase 1), PARK7(Protein DJ1), PARK2(Parkinson juvenile disease protein 2), the glucocerebrosidase (GBA), and ATP(Ezrin-binding protein PACE-1), were sequenced by the use of polymerase chain reaction (PCR) technique. The gene dose of SNCA was checked.Results. There were only two missense mutations observed, respectively, at exon 5 of LRRK2 and exon 10 of PARK2, and both were enrolled in SNPs.Conclusion. No meaningful mutations could be detected, and other susceptibility genes should be detected in FDP patients in China.

Identification and validation of plasma protein biomarker panels for breast cancer diagnosis by using multiple reaction monitoring-based mass spectrometry.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 10621-10621
Author(s):  
Hyeong-Gon Moon ◽  
Un-Beom Kang ◽  
Wonshik Han ◽  
Seock-Ah Im ◽  
Dong-Young Noh
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cancer Diagnosis ◽  
Plasma Protein ◽  
Multiple Reaction Monitoring ◽  
Breast Cancer Diagnosis ◽  
Reaction Monitoring ◽  
Breast Cancer Patients ◽  
Healthy Women ◽  
Protein Signature

10621 Background: Multiple reaction monitoring-based mass spectrometry (MRM-MS) has the ability to perform a wide range of proteome analysis in a single experiment using a small volume of specimen. We aimed to develop a plasma protein signature for breast cancer diagnosis using the MRM-MS technology. Methods: Previously, we have identified lists of breast cancer-related proteins from various models of proteomic discovery including cancer plasma vs healthy plasma, cancer cell line secretome vs non-tumorigenic cell line secretome, cancer tissue vs normal tissue, and literature search. Based on these protein panels, total of 29 proteins were selected for further experiments. We verified and validated the protein signature in two independent cohorts of breast cancer patients and healthy women. Results: In the verification cohort of 80 breast cancer patients and 80 healthy women, MRM-MS showed significant differences in plasma concentration for 11 proteins. Among them, the difference was not significant for 4 proteins when the cases were limited to stage I and II patients. Based on p values and consistent expression level along the AJCC stages, we have created a plasma protein signature comprised of 3 plasma proteins. The 3 plasma protein signature effectively discriminated cancer and healthy cases with the AUC of 0.831 (sensitivity 78.7%, specificity 78.7%). The performance of the 3 plasma protein signature was validated in the cohort of 100 cancer patients and 100 healthy women. The accuracy of the 3 protein signature was still meaningful with the AUC of 0.746 and 0.797 for all stages and stage I or II patients, respectively. Conclusions: The 3 plasma protein signature for breast cancer diagnosis, developed by the MRM-MS technology, showed promising results in the present study.

scholarly journals Crystallizing the Parkinson’s Disease Protein LRRK2 Under Microgravity Conditions

2018 ◽  
Author(s):  
Sebastian Mathea ◽  
Marco Baptista ◽  
Paul Reichert ◽  
April Spinale ◽  
Jian Wu ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
3D Structure ◽  
Space Station ◽  
Rational Drug Design ◽  
Crystal Formation ◽  
Gene Coding ◽  
Rational Drug ◽  
Disease Protein ◽  
Microgravity Conditions

AbstractMutations in the gene coding for leucine-rich repeat kinase 2 (LRRK2) are a considerable cause for Parkinson’s disease (PD). However, the high- resolution 3D structure of the protein is still lacking. This structure will not only help to understand PD etiology but will also enable rational drug design. We have established a reliable method to produce LRRK2 crystals for the first time. However, the limited resolution of the diffraction data prevented structure determination using crystallographic methods. Herein we describe our efforts to improve the crystal quality by crystallizing under microgravity conditions aboard the International Space Station (ISS). Our method features diffusive sample mixing in capillaries and controlled crystal formation by transporting the samples in a frozen state. The crystallisation was successfully repeated under microgravity conditions. However, comparison of earth-grown and microgravity-grown LRRK2 crystals did not reveal any differences in diffraction quality. Here we present the established protocol and our experience adapting crystallization condition to the requirements necessary for successful crystallization of large and sensitive biomolecules under microgravity.

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