Role of Cardiolipin in Mitochondrial Function and Dynamics in Health and Disease: Molecular and Pharmacological Aspects

Cells, Journal Year: 2019, Volume and Issue: 8(7), P. 728 - 728

Published: July 16, 2019

In eukaryotic cells, mitochondria are involved in a large array of metabolic and bioenergetic processes that vital for cell survival. Phospholipids the main building blocks mitochondrial membranes. Cardiolipin (CL) is unique phospholipid which localized synthesized inner membrane (IMM). It now widely accepted CL plays central role many reactions function dynamics. interacts with required optimal activity several IMM proteins, including enzyme complexes electron transport chain (ETC) ATP production their organization into supercomplexes. Moreover, an important morphology, stability dynamics, biogenesis protein import, mitophagy, different steps apoptotic process. conceivable abnormalities content, composition level oxidation may negatively impact implications variety pathophysiological situations diseases. this review, we focus on played by dynamics health diseases potential pharmacological modulation through agents attenuating dysfunction.

Language: Английский

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Gut Microbiota and Metabolome Alterations Associated with Parkinson’s Disease

mSystems, Journal Year: 2020, Volume and Issue: 5(5)

Published: Sept. 14, 2020

Parkinson's disease is a neurodegenerative disorder characterized by the accumulation of intracellular aggregates misfolded alpha-synuclein along cerebral axis. Several studies report association between intestinal dysbiosis and disease, although cause-effect relationship remains to be established. Herein, gut microbiota composition 64 Italian patients with 51 controls was determined using next-generation sequencing approach. A real metagenomics shape based on gas chromatography-mass spectrometry also investigated. The most significant changes within group highlighted reduction in bacterial taxa, which are linked anti-inflammatory/neuroprotective effects, particularly Lachnospiraceae family key members, such as Butyrivibrio, Pseudobutyrivibrio, Coprococcus, Blautia direct evaluation fecal metabolites revealed several classes metabolites. Changes were seen lipids (linoleic acid, oleic succinic sebacic acid), vitamins (pantothenic acid nicotinic amino acids (isoleucine, leucine, phenylalanine, glutamic pyroglutamic acid) other organic compounds (cadaverine, ethanolamine, hydroxy propionic acid). Most modified strongly correlated abundance members belonging family, suggesting that these bacteria correlate altered metabolism rates disease.IMPORTANCE To our knowledge, this one few thus far correlates analysis disease. Overall, data highlight modifications numerous This suggests associated dysregulation involves synergistic microbes favoring homeostasis. Interestingly, short-chain fatty (SCFA)-producing influenced metabolomics profile, affecting potential protective effects Parkinson group. On hand, extensive impact has at level metabolic pathways could encourage identification specific biomarkers for diagnosis treatment light effect drugs have microbiota.

Language: Английский

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Metabolomic profiling reveals the intestinal toxicity of different length of microplastic fibers on zebrafish (Danio rerio)

Journal of Hazardous Materials, Journal Year: 2020, Volume and Issue: 403, P. 123663 - 123663

Published: Aug. 13, 2020

Language: Английский

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Lipid and Lipoprotein Metabolism in Microglia

Frontiers in Physiology, Journal Year: 2020, Volume and Issue: 11

Published: April 28, 2020

Microglia, once viewed as static bystanders with limited homeostatic functions, are now considered key players in the development of neuroinflammatory and neurodegenerative diseases. Microglial activation is a salient feature neuroinflammation involving dynamic process that generates multitudinous microglial phenotypes can respond to variety situational cues central nervous system. Recently, flurry single cell RNA-sequencing studies have defined unprecedented detail, highlighted robust changes expression genes involved lipid lipoprotein metabolism. Increased such Apolipoprotein E (ApoE), Triggering Receptor Expressed on Myeloid Cells 2 (TREM2) Lipoprotein Lipase (LPL) microglia during development, damage, disease, suggest increased metabolism needed fuel protective cellular functions phagocytosis. This review describes our current understanding microglia, highlights modifiable target for treatment diseases Alzheimer's disease multiple sclerosis.

Language: Английский

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Metabolomics of sebum reveals lipid dysregulation in Parkinson’s disease

Nature Communications, Journal Year: 2021, Volume and Issue: 12(1)

Published: March 11, 2021

Parkinson's disease (PD) is a progressive neurodegenerative disorder, which characterised by degeneration of distinct neuronal populations, including dopaminergic neurons the substantia nigra. Here, we use metabolomics profiling approach to identify changes lipids in PD observed sebum, non-invasively available biofluid. We used liquid chromatography-mass spectrometry (LC-MS) analyse 274 samples from participants (80 drug naïve PD, 138 medicated and 56 well matched control subjects) detected metabolites that could predict phenotype. Pathway enrichment analysis shows alterations lipid metabolism related carnitine shuttle, sphingolipid metabolism, arachidonic acid fatty biosynthesis. This study sebum can be potential biomarkers for PD.

Language: Английский

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Metabolic alterations in Parkinson’s disease astrocytes

Scientific Reports, Journal Year: 2020, Volume and Issue: 10(1)

Published: Sept. 2, 2020

Abstract In Parkinson`s disease (PD), the loss of dopaminergic (DA) neurons in substantia nigra pars compacta is associated with Lewy bodies arising from accumulation alpha-synuclein protein which leads ultimately to movement impairment. While PD has been considered a DA neurons, glial contribution, particular that astrocytes, pathogenesis starting be uncovered. Here, we report findings astrocytes derived induced pluripotent stem cells LRRK2 G2019S mutant patients, one patient also carrying GBA N370S mutation, as well healthy individuals. The manifest hallmarks pathology including increased expression alpha-synuclein. This detrimental consequences, resulting altered metabolism, disturbed Ca 2+ homeostasis and release cytokines upon inflammatory stimulation. Furthermore, astroglial levels polyamines polyamine precursors while lysophosphatidylethanolamine are decreased, both these changes have reported brain. Collectively, data reveal an important role for highlight potential iPSC-derived modeling drug discovery.

Language: Английский

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Gut Microbial Ecosystem in Parkinson Disease: New Clinicobiological Insights from Multi‐Omics

Annals of Neurology, Journal Year: 2020, Volume and Issue: 89(3), P. 546 - 559

Published: Dec. 4, 2020

Gut microbiome alterations in Parkinson disease (PD) have been reported repeatedly, but their functional relevance remains unclear. Fecal metabolomics, which provide a readout of microbial activity, scarcely investigated. We investigated fecal and metabolome PD, clinical relevance.Two hundred subjects (104 patients, 96 controls) underwent extensive phenotyping. Stool samples were analyzed using 16S rRNA gene sequencing. metabolomics performed two platforms, nuclear magnetic resonance (NMR) spectroscopy liquid chromatography-mass spectrometry.Fecal composition PD was significantly different from controls, with the largest effect size seen NMR-based metabolome. Microbiome compositional differences remained significant after comprehensive confounder analyses. Differentially abundant metabolite features predicted changes versus controls included bioactive molecules putative neuroprotective effects (eg, short chain fatty acids [SCFAs], ubiquinones, salicylate) other compounds increasingly implicated neurodegeneration ceramides, sphingosine, trimethylamine N-oxide). In group, cognitive impairment, low body mass index (BMI), frailty, constipation, physical activity associated differences. Notably, SCFAs poorer cognition BMI. Lower butyrate levels correlated worse postural instability-gait disorder scores.Gut function is altered characterized by differentially metabolic that important biological insights into gut-brain pathophysiology. Their further supports role for metabolites as potential targets development new biomarkers therapies PD. ANN NEUROL 2021;89:546-559.

Language: Английский

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Brain lipidomics: From functional landscape to clinical significance

Science Advances, Journal Year: 2022, Volume and Issue: 8(37)

Published: Sept. 16, 2022

Lipids are crucial components of cellular function owing to their role in membrane formation, intercellular signaling, energy storage, and homeostasis maintenance. In the brain, lipid dysregulations have been associated with etiology progression neurodegeneration other neurological pathologies. Hence, brain lipids emerging as important potential targets for early diagnosis prognosis diseases. This review aims highlight significance usefulness lipidomics diagnosing treating We explored alterations diseases, paying attention organ-specific characteristics functions lipids. As recent advances would impossible without analytical techniques, we provide up-to-date information on mass spectrometric approaches integrative analysis omic approaches. Last, present applications combined artificial intelligence techniques interdisciplinary collaborative research diseases clinical heterogeneities.

Language: Английский

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Lipid pathway dysfunction is prevalent in patients with Parkinson’s disease

Brain, Journal Year: 2022, Volume and Issue: 145(10), P. 3472 - 3487

Published: May 13, 2022

Abstract Many genetic risk factors for Parkinson’s disease have lipid-related functions and lipid-modulating drugs such as statins may be protective against disease. Moreover, the hallmark pathological protein, α-synuclein, has lipid membrane function pathways dysregulated in endosome–lysosome system synaptic signalling rely heavily on dynamics. Despite potential role lipids disease, most research to date been protein-centric, with large-scale, untargeted serum CSF lipidomic comparisons between idiopathic neurotypical controls limited. In particular, extent which dysregulation occurs mutation carriers of one common genes, LRRK2, is unclear. Further, functional potentially LRRK2 are underexplored. To better determine high-performance liquid chromatography–tandem mass spectrometry was performed (n = 221) 88) obtained from a multi-ethnic population Michael J. Fox Foundation Clinical Cohort Consortium. The cohort consisted controls, asymptomatic G2019S carriers, patients without mutation. Age sex were adjusted analyses where appropriate. Approximately 1000 species per participant analysed. main that distinguished both included ceramide, triacylglycerol, sphingomyelin, acylcarnitine, phosphatidylcholine lysophosphatidylethanolamine. Significant alterations sphingolipids glycerolipids also reflected carrier CSF, although no correlations observed identified CSF. Pathway analysis altered indicated sphingolipid metabolism, insulin mitochondrial major metabolic Importantly, these found samples second 315). Results this study demonstrate generally, functionally metabolically related pathways. These findings provide new insight into dysfunction therapeutics manipulating beneficial patients. profiles novel biomarkers

Language: Английский

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Targeting fatty acid metabolism in glioblastoma

Journal of Clinical Investigation, Journal Year: 2023, Volume and Issue: 133(1)

Published: Jan. 2, 2023

Glioblastoma (GBM) is a primary tumor of the brain defined by its uniform lethality and resistance to conventional therapies. There have been considerable efforts untangle metabolic underpinnings this disease find novel therapeutic avenues for treatment. An emerging focus in field fatty acid (FA) metabolism, which critical numerous diverse biological processes involved GBM pathogenesis. These can be classified into four broad fates: anabolism, catabolism, regulation ferroptosis, generation signaling molecules. Each fate provides unique perspective we inspect biology gives us road map understanding complicated field. This Review discusses basic, translational, clinical insights each these fates provide contemporary FA GBM. It clear, based on literature, that there are far more questions than answers metabolism GBM, substantial should made complex intractable disease.

Language: Английский

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