scholarly journals Ceramide Metabolism and Parkinson’s Disease—Therapeutic Targets

Biomolecules ◽  
2021 ◽  
Vol 11 (7) ◽  
pp. 945
Author(s):  
Antía Custodia ◽  
Marta Aramburu-Núñez ◽  
Clara Correa-Paz ◽  
Adrián Posado-Fernández ◽  
Ana Gómez-Larrauri ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Second Messengers ◽  
Underlying Disease ◽  
Mass Spectrometry Analysis ◽  
Special Focus ◽  
Ionization Mass ◽  
Metabolic Dysfunction ◽  
Spectrometry Analysis ◽  
Cellular Processes

Ceramide is a bioactive sphingolipid involved in numerous cellular processes. In addition to being the precursor of complex sphingolipids, ceramides can act as second messengers, especially when they are generated at the plasma membrane of cells. Its metabolic dysfunction may lead to or be a consequence of an underlying disease. Recent reports on transcriptomics and electrospray ionization mass spectrometry analysis have demonstrated the variation of specific levels of sphingolipids and enzymes involved in their metabolism in different neurodegenerative diseases. In the present review, we highlight the most relevant discoveries related to ceramide and neurodegeneration, with a special focus on Parkinson’s disease.

scholarly journals Metabolomics Fingerprint Induced by the Intranigral Inoculation of Exogenous Human Alpha-Synuclein Oligomers in a Rat Model of Parkinson’s Disease

2020 ◽  
Vol 21 (18) ◽  
pp. 6745
Author(s):  
Federica Murgia ◽  
Luigi Atzori ◽  
Ezio Carboni ◽  
Maria Laura Santoru ◽  
Aran Hendren ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Dehydroascorbic Acid ◽  
Alpha Synuclein ◽  
Mass Spectrometry Analysis ◽  
Substantia Nigra Pars Compacta ◽  
Gas Chromatography Mass Spectrometry ◽  
Serum Samples ◽  
Spectrometry Analysis ◽  
Metabolite Content

Parkinson’s disease (PD) is considered a synucleinopathy because of the intraneuronal accumulation of aggregated α-synuclein (αSyn). Recent evidence points to soluble αSyn-oligomers (αSynO) as the main cytotoxic species responsible for cell death. Given the pivotal role of αSyn in PD, αSyn-based models are crucial for the investigation of toxic mechanisms and the identification of new therapeutic targets in PD. By using a metabolomics approach, we evaluated the metabolic profile of brain and serum samples of rats infused unilaterally with preformed human αSynOs (HαSynOs), or vehicle, into the substantia nigra pars compacta (SNpc). Three months postinfusion, the striatum was dissected for striatal dopamine (DA) measurements via High Pressure Liquid Chromatography (HPLC) analysis and mesencephalon and serum samples were collected for the evaluation of metabolite content via gas chromatography mass spectrometry analysis. Multivariate, univariate and correlation statistics were applied. A 40% decrease of DA content was measured in the HαSynO-infused striatum as compared to the contralateral and the vehicle-infused striata. Decreased levels of dehydroascorbic acid, myo-inositol, and glycine, and increased levels of threonine, were found in the mesencephalon, while increased contents of fructose and mannose, and a decrease in glycine and urea, were found in the serum of HαSynO-infused rats. The significant correlation between DA and metabolite content indicated that metabolic variations reflected the nigrostriatal degeneration. Collectively, the metabolomic fingerprint of HαSynO-infused rats points to an increase of oxidative stress markers, in line with PD neuropathology, and provides hints for potential biomarkers of PD.

scholarly journals Diagnosis of Parkinson’s Disease by A Metabolomics-Based Laboratory-Developed Test (LDT)

Diagnostics ◽  
2020 ◽  
Vol 10 (5) ◽  
pp. 332 ◽  
Author(s):  
Petr G. Lokhov ◽  
Oxana P. Trifonova ◽  
Dmitry L. Maslov ◽  
Steven Lichtenberg ◽  
Elena E. Balashova
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Early Stage ◽  
Mass Spectrometry Analysis ◽  
Great Effort ◽  
Spectrometry Analysis ◽  
Yahr Scale ◽  
In Vitro Diagnostic ◽  
Stage 1

A laboratory-developed test (LDT) is a type of in vitro diagnostic test that is designed, manufactured and used in the same laboratory (i.e., an in-house test). In this study, a metabolomics-based LDT was developed. This test involves a blood plasma preparation, direct-infusion mass spectrometry analysis with a high-resolution mass spectrometer, alignment and normalization of mass peaks using original algorithms, metabolite annotation by a biochemical context-driven algorithm, detection of overrepresented metabolic pathways and results in a visualization in the form of a pathway names cloud. The LDT was applied to detect early stage Parkinson’s disease (PD)—the diagnosis of which currently requires great effort due to the lack of available laboratory tests. In a case–control study (n = 56), the LDT revealed a statistically sound pattern in the PD-relevant pathways. Usage of the LDT for individuals confirmed its ability to reveal this pattern and thus diagnose PD at the early-stage (1–2.5 stages, according to Hoehn and Yahr scale). The detection of this pattern by LDT could diagnose PD with a specificity of 64%, sensitivity of 86% and an accuracy of 75%. Thus, this LDT can be used for further widespread testing.

scholarly journals RasGRP1 is a causal factor in the development of l-DOPA–induced dyskinesia in Parkinson’s disease

2020 ◽  
Vol 6 (18) ◽  
pp. eaaz7001 ◽  
Author(s):  
Mehdi Eshraghi ◽  
Uri Nimrod Ramírez-Jarquín ◽  
Neelam Shahani ◽  
Tommaso Nuzzo ◽  
Arianna De Rosa ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Molecular Mechanisms ◽  
Involuntary Movement ◽  
Mammalian Target Of Rapamycin ◽  
Mass Spectrometry Analysis ◽  
Therapeutic Effects ◽  
Nucleotide Exchange ◽  
Spectrometry Analysis ◽  
Macaque Model

The therapeutic effects of l-3,4-dihydroxyphenylalanine (l-DOPA) in patients with Parkinson’s disease (PD) severely diminishes with the onset of abnormal involuntary movement, l-DOPA–induced dyskinesia (LID). However, the molecular mechanisms that promote LID remain unclear. Here, we demonstrated that RasGRP1 [(guanine nucleotide exchange factor (GEF)] controls the development of LID. l-DOPA treatment rapidly up-regulated RasGRP1 in the striatum of mouse and macaque model of PD. The lack of RasGRP1 in mice (RasGRP1−/−) dramatically diminished LID without interfering with the therapeutic effects of l-DOPA. Besides acting as a GEF for Ras homolog enriched in the brain (Rheb), the activator of the mammalian target of rapamycin kinase (mTOR), RasGRP1 promotes l-DOPA–induced extracellular signal-regulated kinase (ERK) and the mTOR signaling in the striatum. High-resolution tandem mass spectrometry analysis revealed multiple RasGRP1 downstream targets linked to LID vulnerability. Collectively, the study demonstrated that RasGRP1 is a critical striatal regulator of LID.

scholarly journals Hypoxia, Acidification and Inflammation: Partners in Crime in Parkinson’s Disease Pathogenesis?

Immuno ◽  
2021 ◽  
Vol 1 (2) ◽  
pp. 78-90
Author(s):  
Johannes Burtscher ◽  
Grégoire P. Millet
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Neurodegenerative Diseases ◽  
Current Knowledge ◽  
Cell Types ◽  
Brain Cell ◽  
Special Focus ◽  
Molecular Alterations ◽  
Research Fields

Like in other neurodegenerative diseases, protein aggregation, mitochondrial dysfunction, oxidative stress and neuroinflammation are hallmarks of Parkinson’s disease (PD). Differentiating characteristics of PD include the central role of α-synuclein in the aggregation pathology, a distinct vulnerability of the striato-nigral system with the related motor symptoms, as well as specific mitochondrial deficits. Which molecular alterations cause neurodegeneration and drive PD pathogenesis is poorly understood. Here, we summarize evidence of the involvement of three interdependent factors in PD and suggest that their interplay is likely a trigger and/or aggravator of PD-related neurodegeneration: hypoxia, acidification and inflammation. We aim to integrate the existing knowledge on the well-established role of inflammation and immunity, the emerging interest in the contribution of hypoxic insults and the rather neglected effects of brain acidification in PD pathogenesis. Their tight association as an important aspect of the disease merits detailed investigation. Consequences of related injuries are discussed in the context of aging and the interaction of different brain cell types, in particular with regard to potential consequences on the vulnerability of dopaminergic neurons in the substantia nigra. A special focus is put on the identification of current knowledge gaps and we emphasize the importance of related insights from other research fields, such as cancer research and immunometabolism, for neurodegeneration research. The highlighted interplay of hypoxia, acidification and inflammation is likely also of relevance for other neurodegenerative diseases, despite disease-specific biochemical and metabolic alterations.

Dereplication of Bromotyrosine-derived Metabolites by LC-PDA-MS and Analysis of the Chemical Profile of 14 Aplysina Sponge Specimens from the Brazilian Coastline

2010 ◽  
Vol 63 (6) ◽  
pp. 886 ◽  
Author(s):  
Michelli M. Silva ◽  
Juliana Bergamasco ◽  
Simone P. Lira ◽  
Norberto P. Lopes ◽  
Eduardo Hajdu ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Electrospray Ionization ◽  
Electrospray Ionization Mass Spectrometry ◽  
Marine Sponges ◽  
Mass Spectrometry Analysis ◽  
Ionization Mass ◽  
Chemical Profile ◽  
Spectrometry Analysis ◽  
Ion Clusters ◽  
Single Compound

In order to investigate the chemical profile of 14 specimens of Aplysina spp. marine sponges, we have developed a method based on LC-PDA-MS for the detection of bromotyrosine-derived metabolites. The method enabled the dereplication of three distinct chemotypes of bromotyrosine-derived compounds based on UV absorptions, which were further refined by electrospray ionization-mass spectrometry analysis of the brominated quasi-molecular ion clusters. This procedure led to either a single compound assignment, or a maximum of two possible isobaric compounds. The dereplication study indicated that the chemical profile of the 14 specimens of Aplysina spp. analyzed presented practically the same dibromotyrosine-derived compounds. The results obtained suggested a possible biogenetic pathway for the formation of dibromotyrosine-derived compounds of wide occurrence in Verongida sponges.

scholarly journals Characterization of anthocyanin from red sorghum (Sorghum bicolor) bran by liquid chromatography-electron spray ionization mass spectrometry analysis

2021 ◽  
pp. 146906672110357
Author(s):  
P Suganyadevi ◽  
M Saravanakumar ◽  
S Mohandas
Keyword(s):  
Mass Spectrometry ◽  
Liquid Chromatography ◽  
Sorghum Bicolor ◽  
Mass Spectrometry Analysis ◽  
Ionization Mass Spectrometry ◽  
Published Data ◽  
Ionization Mass ◽  
Spectrometric Data ◽  
Spectrometry Analysis ◽  
Sorghum Bran

In the present study, anthocyanin pigments from red sorghum ( Sorghum bicolor) bran were identified and characterized by Liquid Chromatography-Electron Spray Ionization Mass Spectrometry. The individual anthocyanins were identified by comparing their mass spectrometric data and retention times, published data. 3-deoxyanthocyanidins and methyl 3-deoxyanthocyanidins were identified in red sorghum bran. This paper presents complete LCMS profile and MS spectrometric data of red sorghum bran.

scholarly journals Selective Capture and Identification of Methicillin-Resistant Staphylococcus aureus by Combining Aptamer-Modified Magnetic Nanoparticles and Mass Spectrometry

2021 ◽  
Vol 22 (12) ◽  
pp. 6571
Author(s):  
Yu-Chen Liu ◽  
Katragunta Kumar ◽  
Cheng-Hsiu Wu ◽  
Kai-Chih Chang ◽  
Cheng-Kang Chiang ◽  
...  
Keyword(s):  
Mass Spectrometry ◽  
Staphylococcus Aureus ◽  
Magnetic Nanoparticles ◽  
Methicillin Resistant Staphylococcus Aureus ◽  
Capture Rate ◽  
Mass Spectrometry Analysis ◽  
Ionization Mass ◽  
Methicillin Resistant ◽  
Spectrometry Analysis ◽  
Modified Magnetic Nanoparticles

A nucleic acid aptamer that specifically recognizes methicillin-resistant Staphylococcus aureus (MRSA) has been immobilized on magnetic nanoparticles to capture the target bacteria prior to mass spectrometry analysis. After the MRSA species were captured, they were further eluted from the nanoparticles and identified using matrix-assisted laser desorption ionization mass spectrometry (MALDI-MS). The combination of aptamer-based capture/enrichment and MS analysis of microorganisms took advantage of the selectivity of both techniques and should enhance the accuracy of MRSA identification. The capture and elution efficiencies for MRSA were optimized by examining factors such as incubation time, temperature, and elution solvents. The aptamer-modified magnetic nanoparticles showed a capture rate of more than 90% under the optimized condition, whereas the capture rates were less than 11% for non-target bacteria. The as-prepared nanoparticles exhibited only a 5% decrease in the capture rate and a 9% decrease in the elution rate after 10 successive cycles of utilization. Most importantly, the aptamer-modified nanoparticles revealed an excellent selectivity towards MRSA in bacterial mixtures. The capture of MRSA at a concentration of 102 CFU/mL remained at a good percentage of 82% even when the other two species were at 104 times higher concentration (106 CFU/mL). Further, the eluted MRSA bacteria were successfully identified using MALDI mass spectrometry.

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