scholarly journals Inside Cover: Autoproteolytic Fragments Are Intermediates in the Oligomerization/Aggregation of the Parkinson's Disease Protein Alpha-Synuclein as Revealed by Ion Mobility Mass Spectrometry (ChemBioChem 18/2011)

ChemBioChem ◽  
2011 ◽  
Vol 12 (18) ◽  
pp. 2706-2706
Author(s):  
Camelia Vlad ◽  
Kathrin Lindner ◽  
Christiaan Karreman ◽  
Stefan Schildknecht ◽  
Marcel Leist ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ion Mobility ◽  
Alpha Synuclein ◽  
Ion Mobility Mass Spectrometry ◽  
Disease Protein

Rapid Diagnosis of Parkinson’s Disease from Sebum using Paper Spray Ionisation Ion Mobility Mass Spectrometry

2020 ◽  
Author(s):  
Depanjan Sarkar ◽  
Drupad Trivedi ◽  
Eleanor Sinclair ◽  
Sze Hway Lim ◽  
Caitlin Walton-Doyle ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ion Mobility ◽  
Neurodegenerative Disorder ◽  
Treatment Options ◽  
Ion Mobility Mass Spectrometry ◽  
Paper Spray ◽  
Molecular Features ◽  
Validation Set

Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which identification of robust biomarkers to complement clinical PD diagnosis would accelerate treatment options and help to stratify disease progression. Here we demonstrate the use of paper spray ionisation coupled with ion mobility mass spectrometry (PSI IM-MS) to determine diagnostic molecular features of PD in sebum. PSI IM-MS was performed directly from skin swabs, collected from 34 people with PD and 30 matched control subjects as a training set and a further 91 samples from 5 different collection sites as a validation set. PSI IM-MS elucidates ~ 4200 features from each individual and we report two classes of lipids (namely phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD. Putative metabolite annotations are obtained using tandem mass spectrometry experiments combined with accurate mass measurements. Sample preparation and PSI IM-MS analysis and diagnosis can be performed ~5 minutes per sample offering a new route to for rapid and inexpensive confirmatory diagnosis of this disease.

Rapid Diagnosis of Parkinson’s Disease from Sebum using Paper Spray Ionisation Ion Mobility Mass Spectrometry

2020 ◽  
Author(s):  
Depanjan Sarkar ◽  
Drupad Trivedi ◽  
Eleanor Sinclair ◽  
Sze Hway Lim ◽  
Caitlin Walton-Doyle ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ion Mobility ◽  
Neurodegenerative Disorder ◽  
Treatment Options ◽  
Ion Mobility Mass Spectrometry ◽  
Paper Spray ◽  
Molecular Features ◽  
Validation Set

Parkinson’s disease (PD) is the second most common neurodegenerative disorder for which identification of robust biomarkers to complement clinical PD diagnosis would accelerate treatment options and help to stratify disease progression. Here we demonstrate the use of paper spray ionisation coupled with ion mobility mass spectrometry (PSI IM-MS) to determine diagnostic molecular features of PD in sebum. PSI IM-MS was performed directly from skin swabs, collected from 34 people with PD and 30 matched control subjects as a training set and a further 91 samples from 5 different collection sites as a validation set. PSI IM-MS elucidates ~ 4200 features from each individual and we report two classes of lipids (namely phosphatidylcholine and cardiolipin) that differ significantly in the sebum of people with PD. Putative metabolite annotations are obtained using tandem mass spectrometry experiments combined with accurate mass measurements. Sample preparation and PSI IM-MS analysis and diagnosis can be performed ~5 minutes per sample offering a new route to for rapid and inexpensive confirmatory diagnosis of this disease.

scholarly journals Paper Spray Ionisation Ion Mobility Mass Spectrometry of Sebum Classifies Biomarker Classes for the Diagnosis of Parkinson’s Disease

2021 ◽  
Author(s):  
Depanjan Sarkar ◽  
Eleanor Sinclair ◽  
Sze Hway Lim ◽  
Caitlin Walton-Doyle ◽  
Kaneez Jafri ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Ion Mobility ◽  
Neurodegenerative Disorder ◽  
Collision Cross Section ◽  
Treatment Options ◽  
Ion Mobility Mass Spectrometry ◽  
Direct Infusion ◽  
Paper Spray

Parkinson’s disease (PD) is the second most common neurodegenerative disorder and identification of robust biomarkers to complement clinical diagnosis will accelerate treatment options. Here we demonstrate the use of direct infusion of sebum from skin swabs using paper spray ionisation coupled with ion mobility mass spectrometry (PS-IM-MS) to determine the regulation of molecular classes of lipids in sebum that are diagnostic of PD. A PS-IM-MS method for sebum samples that takes three minutes per swab was developed and optimised. The method was applied to skin swabs collected from 150 people and elucidates ~ 4200 features from each subject which were independently analysed. The data included high molecular weight lipids (>600 Da.) that differ significantly in the sebum of people with PD. Putative metabolite annotations of several lipid classes, predominantly triglycerides and larger acyl glycerides, were obtained using accurate mass, tandem mass spectrometry and collision cross section measurements.

Ion Mobility Mass Spectrometry Studies of the Inhibition of Alpha Synuclein Amyloid Fibril Formation by ( - )-Epigallocatechin-3-Gallate

2011 ◽  
Vol 64 (1) ◽  
pp. 36 ◽  
Author(s):  
Yanqin Liu ◽  
Lam H. Ho ◽  
John. A. Carver ◽  
Tara L. Pukala
Keyword(s):  
Mass Spectrometry ◽  
Conformational Change ◽  
Ion Mobility ◽  
Amyloid Fibril ◽  
Heterogeneous Systems ◽  
Alpha Synuclein ◽  
Fibril Formation ◽  
Ion Mobility Mass Spectrometry ◽  
Compact Structure ◽  
Amyloid Fibril Formation

Ion mobility-mass spectrometry (IM-MS) is emerging as an important biophysical technique for the structural analysis of proteins and their assemblies, in particular for structurally heterogeneous systems such as those on the protein misfolding and aggregation pathway. Using IM-MS we have monitored amyloid fibril formation of A53T α-synuclein, a mutant synuclein protein associated with Parkinson’s disease, and identified that a conformational change towards a more compact structure occurs during the initial stages of aggregation. Binding of A53T α-synuclein to a flavenoid based amyloid fibril inhibitor, (–)-epigallocatechin-3-gallate, has been observed with a 1:1 stoichiometry. By analysis of ion collision cross-sections, we show epigallocatechin gallate binding prevents protein conformational change, and in turn decreases the formation of fibrillar aggregates.

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.

scholarly journals Protein unfolding in freeze frames: intermediate states are revealed by variable temperature ion mobility-mass spectrometry.

2021 ◽  
Author(s):  
Jakub Ujma ◽  
Jacquelyn Jhingree ◽  
Emma Norgate ◽  
Rosie Upton ◽  
Xudong Wang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Ion Mobility ◽  
Elevated Temperatures ◽  
Alpha Synuclein ◽  
Conformational Space ◽  
Disordered Proteins ◽  
Reduced Form ◽  
Ion Mobility Mass Spectrometry ◽  
Model Framework ◽  
Intermediate States

The gas phase is an idealized laboratory for the study of protein structure, from which it is possible to examine stable and transient forms of mass selected ions in the absence of bulk solvent. With ion mobility-mass spectrometry (IM-MS) apparatus built to operate at both cryogenic and elevated temperatures, we have examined the conformational transitions of the monomeric proteins: ubiquitin, lysozyme and alpha-synuclein as a function of temperature and in source activation. We rationalize the experimental observations with a temperature dependent framework model and comparison to known conformers. Data from ubiquitin shows unfolding transitions that proceed through diverse and highly elongated intermediate states, which converge to more compact structures. These findings contrast with data obtained from lysozyme – a protein where (un)-folding plasticity is restricted by four disulfide linkages, although this is alleviated in its reduced form. For structured proteins, collision activation of the protein ions in- source, enables subsequent “freezing” or thermal annealing of unfolding intermediates whereas disordered proteins restructure substantially at 250 K even without activation, indicating that cold denaturation can occur without solvent. These data are presented in the context of a toy model framework which describes the relative occupancy of the available conformational space.

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