scholarly journals Lipotoxicity Downstream of α-Synuclein Imbalance: A Relevant Pathomechanism in Synucleinopathies?

Biomolecules ◽  
2021 ◽  
Vol 12 (1) ◽  
pp. 40
Author(s):  
Arati Tripathi ◽  
Saranna Fanning ◽  
Ulf Dettmer
Keyword(s):  
Fatty Acids ◽  
Neuronal Loss ◽  
Brain Diseases ◽  
Neuronal Protein ◽  
Lipid Species ◽  
A Cell ◽  
Experimental Approaches ◽  
Toxicity Mechanisms ◽  
Insight Into ◽  
Storage Disorders

Neuronal loss in Parkinson’s disease and related brain diseases has been firmly linked to the abundant neuronal protein α-synuclein (αS). However, we have gained surprisingly little insight into how exactly αS exerts toxicity in these diseases. Hypotheses of proteotoxicity, disturbed vesicle trafficking, mitochondrial dysfunction and other toxicity mechanisms have been proposed, and it seems possible that a combination of different mechanisms may drive pathology. A toxicity mechanism that has caught increased attention in the recent years is αS-related lipotoxicity. Lipotoxicity typically occurs in a cell when fatty acids exceed the metabolic needs, triggering a flux into harmful pathways of non-oxidative metabolism. Genetic and experimental approaches have revealed a significant overlap between lipid storage disorders, most notably Gaucher’s disease, and synucleinopathies. There is accumulating evidence for lipid aberrations causing synuclein misfolding as well as for αS excess and misfolding causing lipid aberration. Does that mean the key problem in synucleinopathies is lipotoxicity, the accumulation of harmful lipid species or alteration in lipid equilibrium? Here, we review the existing literature in an attempt to get closer to an answer.

scholarly journals Heat stress elicits remodeling in the anther lipidome of peanut

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zolian S. Zoong Lwe ◽  
Ruth Welti ◽  
Daniel Anco ◽  
Salman Naveed ◽  
Sachin Rustgi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Heat Stress ◽  
Fatty Acid ◽  
Membrane Lipids ◽  
Fatty Acid Desaturase ◽  
Susceptible Genotype ◽  
Unsaturated Lipid ◽  
Lipid Species ◽  
Lipid Unsaturation ◽  
Fatty Acid Amount

AbstractUnderstanding the changes in peanut (Arachis hypogaea L.) anther lipidome under heat stress (HT) will aid in understanding the mechanisms of heat tolerance. We profiled the anther lipidome of seven genotypes exposed to ambient temperature (AT) or HT during flowering. Under AT and HT, the lipidome was dominated by phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TAG) species (> 50% of total lipids). Of 89 lipid analytes specified by total acyl carbons:total carbon–carbon double bonds, 36:6, 36:5, and 34:3 PC and 34:3 PE (all contain 18:3 fatty acid and decreased under HT) were the most important lipids that differentiated HT from AT. Heat stress caused decreases in unsaturation indices of membrane lipids, primarily due to decreases in highly-unsaturated lipid species that contained 18:3 fatty acids. In parallel, the expression of Fatty Acid Desaturase 3-2 (FAD3-2; converts 18:2 fatty acids to 18:3) decreased under HT for the heat-tolerant genotype SPT 06-07 but not for the susceptible genotype Bailey. Our results suggested that decreasing lipid unsaturation levels by lowering 18:3 fatty-acid amount through reducing FAD3 expression is likely an acclimation mechanism to heat stress in peanut. Thus, genotypes that are more efficient in doing so will be relatively more tolerant to HT.

scholarly journals Quantification of Dendritic Spines Remodeling under Physiological Stimuli and in Pathological Conditions

2021 ◽  
Vol 22 (8) ◽  
pp. 4053
Author(s):  
Ewa Bączyńska ◽  
Katarzyna Karolina Pels ◽  
Subhadip Basu ◽  
Jakub Włodarczyk ◽  
Błażej Ruszczycki
Keyword(s):  
Dendritic Spines ◽  
Quantitative Data ◽  
Statistical Significance ◽  
Brain Diseases ◽  
Synaptic Connections ◽  
Brain Pathology ◽  
Biological Models ◽  
Structural Geometry ◽  
Pathological Conditions ◽  
Experimental Approaches

Numerous brain diseases are associated with abnormalities in morphology and density of dendritic spines, small membranous protrusions whose structural geometry correlates with the strength of synaptic connections. Thus, the quantitative analysis of dendritic spines remodeling in microscopic images is one of the key elements towards understanding mechanisms of structural neuronal plasticity and bases of brain pathology. In the following article, we review experimental approaches designed to assess quantitative features of dendritic spines under physiological stimuli and in pathological conditions. We compare various methodological pipelines of biological models, sample preparation, data analysis, image acquisition, sample size, and statistical analysis. The methodology and results of relevant experiments are systematically summarized in a tabular form. In particular, we focus on quantitative data regarding the number of animals, cells, dendritic spines, types of studied parameters, size of observed changes, and their statistical significance.

scholarly journals Insight into the Secondary Metabolites of Geum urbanum L. and Geum rivale L. Seeds (Rosaceae)

Plants ◽  
2021 ◽  
Vol 10 (6) ◽  
pp. 1219
Author(s):  
Marek Bunse ◽  
Peter Lorenz ◽  
Florian C. Stintzing ◽  
Dietmar R. Kammerer
Keyword(s):  
Fatty Acids ◽  
Phenolic Compounds ◽  
Unsaturated Fatty Acids ◽  
Asiatic Acid ◽  
Cosmetic Products ◽  
Nutritional Properties ◽  
First Time ◽  
Derivatives Of ◽  
Geum Urbanum ◽  
Insight Into

The present study aimed at the identification and quantitation of phenolic compounds, fatty acids, and further characteristic substances in the seeds of Geum urbanum L. and Geum rivale L. For this purpose, individual components of extracts recovered with MeOH, CH2Cl2, and by cold-pressing, respectively, were characterized by HPLC-DAD/ESI-MSn and GC/MS and compared with reference compounds. For both Geum species, phenolic compounds, such as flavonoids and gallic acid derivatives, and triterpenes, such as saponins and their aglycones, were detected. Surprisingly, both Geum species revealed the presence of derivatives of the triterpenoid aglycons asiatic acid and madecassic acid, which were characterized for the first time in the genus Geum. Furthermore, the fatty acids of both species were characterized by GC–MS after derivatization. Both species showed a promising fatty-acid profile in terms of nutritional properties because of high proportions of unsaturated fatty acids. Linoleic acid and linolenic acid were most abundant, among other compounds such as palmitic acid and stearic acid. In summary, the present study demonstrates the seeds of G. urbanum and G. rivale to be a valuable source of unsaturated fatty acids and bioactive phenolics, which might be exploited for nutritional and cosmetic products and for phytotherapeutic purposes.

scholarly journals Lipidomics Provides New Insight into Pathogenesis and Therapeutic Targets of the Ischemia—Reperfusion Injury

2021 ◽  
Vol 22 (6) ◽  
pp. 2798
Author(s):  
Zoran Todorović ◽  
Siniša Đurašević ◽  
Maja Stojković ◽  
Ilijana Grigorov ◽  
Slađan Pavlović ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Time Course ◽  
Membrane Lipids ◽  
Lipid Analysis ◽  
Cell Damage ◽  
Ischemia Reperfusion ◽  
Enzyme Inactivation ◽  
Critical Event ◽  
Tissue Ischemia ◽  
Insight Into

Lipids play an essential role in both tissue protection and damage. Tissue ischemia creates anaerobic conditions in which enzyme inactivation occurs, and reperfusion can initiate oxidative stress that leads to harmful changes in membrane lipids, the formation of aldehydes, and chain damage until cell death. The critical event in such a series of harmful events in the cell is the unwanted accumulation of fatty acids that leads to lipotoxicity. Lipid analysis provides additional insight into the pathogenesis of ischemia/reperfusion (I/R) disorders and reveals new targets for drug action. The profile of changes in the composition of fatty acids in the cell, as well as the time course of these changes, indicate both the mechanism of damage and new therapeutic possibilities. A therapeutic approach to reperfusion lipotoxicity involves attenuation of fatty acids overload, i.e., their transport to adipose tissue and/or inhibition of the adverse effects of fatty acids on cell damage and death. The latter option involves using PPAR agonists and drugs that modulate the transport of fatty acids via carnitine into the interior of the mitochondria or the redirection of long-chain fatty acids to peroxisomes.

Combining computational and experimental approaches to select chromophores to enable the detection of fatty acids via HPLC

2019 ◽  
Vol 11 (23) ◽  
pp. 2952-2959 ◽  
Author(s):  
Jessica Pandohee ◽  
Robert J. Rees ◽  
Michelle J. S. Spencer ◽  
Aaron Raynor ◽  
Oliver A. H. Jones
Keyword(s):  
Fatty Acids ◽  
Quantum Mechanics ◽  
Chemical Reaction ◽  
Experimental Approaches ◽  
Systematic Selection ◽  
Selection Of

This paper outlines a protocol, which combines quantum mechanics calculations and experimental synthesis, to enable systematic selection of suitable chromophores based on their stability of fluorescence and efficiency of the chemical reaction.

scholarly journals New Insights on the Mechanism of Fatty Acids as Buccal Permeation Enhancers

Pharmaceutics ◽  
2018 ◽  
Vol 10 (4) ◽  
pp. 201 ◽  
Author(s):  
Cristina Padula ◽  
Silvia Pescina ◽  
Sara Nicoli ◽  
Patrizia Santi
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Fluorescein Isothiocyanate ◽  
Penetration Enhancers ◽  
Systemic Delivery ◽  
Permeation Enhancers ◽  
Maximum Value ◽  
The Relationship ◽  
Insight Into ◽  
The Ideal

Buccal mucosa has recently received much attention as a potential route for systemic delivery of drugs, including biologics and vaccines. The aim of this work was to gain insight into the mechanism of fatty acids as buccal permeation enhancers, by studying the effect of a series of medium and long chain fatty acids on the permeation of a model high molecular weight and hydrophilic molecule, fluorescein isothiocyanate labelled dextran (FD-4, m.w. 4 kDa) across porcine esophageal epithelium. A parabolic relationship between fatty acid lipophilicity and enhancement was obtained, regardless of the presence and number of double bonds. The relationship, which resembles the well-known relationship between permeability and lipophilicity of transdermal delivery, presents a maximum value in correspondence of C10 (logP approx. 4). This is probably the ideal lipophilicity for the fatty acid to interact with the lipid domains of the mucosa. When the same analysis was performed on skin data, the same trend was observed, although the maximum value was reached for C12 (logP approx. 5), in agreement with the higher lipophilicity of the skin. The results obtained in the present work represent a significant advancement in the understanding of the mechanisms of action of fatty acids as buccal penetration enhancers.

scholarly journals Solvent selection for fatty acid residue analysis of archeologicial artifacts

2017 ◽  
Vol 3 (1) ◽  
pp. 1-10
Author(s):  
Jeffrey J. Rosentreter ◽  
John Malamakal ◽  
Kelli Barnes ◽  
Matt Alexander
Keyword(s):  
Fatty Acids ◽  
Extraction Efficiency ◽  
Lipid Analysis ◽  
Residue Analysis ◽  
Chemical Properties ◽  
Fatty Acid Residue ◽  
Quantitative Extraction ◽  
Selection For ◽  
Carbonized Wood ◽  
Insight Into

AbstractResidue analysis has rapidly become one of the most useful techniques for determining an artifact function and revealing insight into paleodiets. The success of analytical residue analysis often lies with the first preparatory step, where the residue is extracted from the object. Detection of a residue requires effective solvation of the material, and there is a large range of potential solvents. One purpose of this study is to determine the efficiency of various solvents for the extraction of fatty acids from charcoal, a material that is ubiquitous, easily identified, remarkably stable in the archaeological record but, most importantly for this research, retains fats extremely well. This investigation examines the removal efficiency of model fatty acids from carbonized wood samples. The strong affinity of lipids to charcoal makes carbonized wood ideal for retaining them, but also makes their extraction extremely challenging and thus an ideal benchmark for solvent extraction characterization. Several solvents (benzene, chloroform, hexane, methanol and water) are used to determine the quantitative extraction efficiency of tripalmitin. While benzene and chloroform perform best for some wood types, neither solvent is better for all carbonized wood. Correlations between the chemical properties of the solvents and the effectiveness of the extraction provide guidance for solvents. Findings indicate solvent characteristics including dipole moment, dielectric constant, hydrogen bonding, and molecular weight all play an important role in extraction of fat from a charcoal matrix. Results presented should provide guidelines to allow for more effective residue extration and more accurate lipid analysis.

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