Tibolone Pre-Treatment Ameliorates the Dysregulation of Protein Translation and Transport Generated by Palmitic Acid-Induced Lipotoxicity in Human Astrocytes: A Label-Free MS-Based Proteomics and Network Analysis DOI Open Access
Diego Julián Vesga-Jiménez, Cynthia Martín-Jiménez, Adriana Grismaldo

et al.

International Journal of Molecular Sciences, Journal Year: 2022, Volume and Issue: 23(12), P. 6454 - 6454

Published: June 9, 2022

Excessive accumulation and release of fatty acids (FAs) in adipose non-adipose tissue are characteristic obesity associated with the leading causes death worldwide. Chronic exposure to high concentrations FAs such as palmitic acid (pal) is a risk factor for developing different neurodegenerative diseases (NDs) through several mechanisms. In brain, astrocytic dysregulation plays an essential role detrimental processes like metabolic inflammatory state, oxidative stress, endoplasmic reticulum autophagy impairment. Evidence shows that tibolone, synthetic steroid, induces neuroprotective effects, but its molecular mechanisms upon pal remain largely unknown. Due capacity identifying changes whole data-set proteins their interaction allowing deeper understanding, we used proteomic approach on normal human astrocytes under supraphysiological levels model induce cytotoxicity, finding expression related translation, transport, autophagy, apoptosis. Additionally, tibolone pre-treatment showed protective effects by restoring those same pal-altered increasing from cell survival processes. Interestingly, ARF3 IPO7 were identified relevant proteins, presenting weight protein-protein network significant differences levels. These transport translation processes, was restored tibolone. This work suggests damage caused simultaneously involves can partially revert, making interesting further research understand how modulate these damages.

Language: Английский

Type 2 Diabetes and Alzheimer’s Disease: The Emerging Role of Cellular Lipotoxicity DOI Creative Commons
Nicola Marrano, Giuseppina Biondi, Anna Borrelli

et al.

Biomolecules, Journal Year: 2023, Volume and Issue: 13(1), P. 183 - 183

Published: Jan. 16, 2023

Type 2 diabetes (T2D) and Alzheimer’s diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates AD is a significant comorbidity of T2D, there ~1.4–2-fold increase risk developing among T2D patients, involvement possible common triggers pathogenesis these two remains largely unknown. Of note, recent mechanistic insights suggest lipotoxicity could missing ring pathogenetic mechanisms linking to AD. Indeed, obesity, which represents main cause lipotoxicity, has been recognized as factor for both pathological conditions. Lipotoxicity can lead inflammation, insulin resistance, oxidative stress, ceramide amyloid accumulation, endoplasmic reticulum ferroptosis, autophagy, are shared biological events In current review, we try provide critical comprehensive view molecular pathways activated by AD, attempting summarize how drive future research open way new therapeutic perspectives.

Language: Английский

Citations

26
S-Palmitoylation of Synaptic Proteins in Neuronal Plasticity in Normal and Pathological Brains DOI Creative Commons
Anna Buszka,

Agata Pytyś,

Domnic Colvin

et al.

Cells, Journal Year: 2023, Volume and Issue: 12(3), P. 387 - 387

Published: Jan. 21, 2023

Protein lipidation is a common post-translational modification of proteins that plays an important role in human physiology and pathology. One form protein lipidation, S-palmitoylation, involves the addition 16-carbon fatty acid (palmitate) onto proteins. This reversible may affect regulation trafficking stability membranes. From multiple recent experimental studies, picture emerges whereby S-palmitoylation ubiquitous yet discrete molecular switch enabling expansion functions subcellular localization minutes to hours. Neural tissue particularly rich are regulated by S-palmitoylation. A surge novel methods detection at high resolution allowed us get better insights into roles palmitoylation brain pathophysiology. In this review, we specifically discuss work devoted understanding impact on functional changes excitatory inhibitory synapses associated with neuronal activity plasticity. The accumulated evidence also implies crucial learning memory, disorders impaired cognitive functions.

Language: Английский

Citations

18
Alterations of the blood-brain barrier during aging DOI

Yufan Cao,

Weihai Xu,

Qing Liu

et al.

Journal of Cerebral Blood Flow & Metabolism, Journal Year: 2024, Volume and Issue: 44(6), P. 881 - 895

Published: March 21, 2024

The blood-brain barrier (BBB) is a complex and dynamic interface that regulates the exchange of molecules cells between blood central nervous system. It undergoes structural functional changes during aging, which may compromise its integrity contribute to pathogenesis neurodegenerative diseases. In recent years, advances in microscopy high-throughput bioinformatics have allowed more in-depth investigation aging mechanisms BBB. This review summarizes age-related alterations BBB structure function from six perspectives: endothelial cells, astrocytes, pericytes, basement membrane, microglia perivascular macrophages, fibroblasts, ranging molecular level human multi-system level. These basic components are essential for proper functioning Recent imaging methods were also reviewed. Elucidation age-associated offer insights into homeostasis provide effective therapeutic strategies protect it aging.

Language: Английский

Citations

8
Metabolic Contrasts: Fatty Acid Oxidation and Ketone Bodies in Healthy Brains vs. Glioblastoma Multiforme DOI Open Access
Flaviu Tămaș, Flaviu Tămaș, Attila Kövecsi

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(10), P. 5482 - 5482

Published: May 17, 2024

The metabolism of glucose and lipids plays a crucial role in the normal homeostasis body. Although is main energy substrate, its absence, lipid becomes primary source energy. means fatty acid oxidation (FAO) takes place mitochondrial matrix through β-oxidation. Glioblastoma (GBM) most common form malignant brain tumor (45.6%), with an incidence 3.1 per 100,000. metabolic changes found GBM cells surrounding microenvironment are associated proliferation, migration, resistance to treatment. Tumor show remodeling use glycolysis at expense oxidative phosphorylation (OXPHOS), known as Warburg effect. Specialized acids (FAs) transporters such FAT, FABP, or FATP from overexpressed contribute absorption storage increased amount that will provide sufficient used for growth invasion. This review provides overview key enzymes, transporters, regulatory pathways FAs ketone bodies (KBs) versus cells, highlighting need develop new therapeutic strategies improve treatment efficacy patients GBM.

Language: Английский

Citations

8
A crazy trio in Parkinson's disease: metabolism alteration, α-synuclein aggregation, and oxidative stress DOI

Sheng Li,

Yanbing Liu, Sen Lu

et al.

Molecular and Cellular Biochemistry, Journal Year: 2024, Volume and Issue: unknown

Published: April 16, 2024

Language: Английский

Citations

7
Anti-Parkinson Effects of Holothuria leucospilota-Derived Palmitic Acid in Caenorhabditis elegans Model of Parkinson’s Disease DOI Creative Commons

Tanatcha Sanguanphun,

Sukrit Promtang,

Nilubon Sornkaew

et al.

Marine Drugs, Journal Year: 2023, Volume and Issue: 21(3), P. 141 - 141

Published: Feb. 23, 2023

Parkinson's disease (PD) is the second most common neurodegenerative which still incurable. Sea cucumber-derived compounds have been reported to be promising candidate drugs for treating age-related neurological disorders. The present study evaluated beneficial effects of Holothuria leucospilota (H. leucospilota)-derived compound 3 isolated from ethyl acetate fraction (HLEA-P3) using Caenorhabditis elegans PD models. HLEA-P3 (1 50 µg/mL) restored viability dopaminergic neurons. Surprisingly, 5 and 25 µg/mL improved dopamine-dependent behaviors, reduced oxidative stress prolonged lifespan worms induced by neurotoxin 6-hydroxydopamine (6-OHDA). Additionally, (5 decreased α-synuclein aggregation. Particularly, locomotion, lipid accumulation extended transgenic C. strain NL5901. Gene expression analysis revealed that treatment with could upregulate genes encoding antioxidant enzymes (gst-4, gst-10 gcs-1) autophagic mediators (bec-1 atg-7) downregulate fatty acid desaturase gene (fat-5). These findings explained molecular mechanism HLEA-P3-mediated protection against PD-like pathologies. chemical characterization elucidated palmitic acid. Taken together, these anti-Parkinson H. leucospilota-derived in 6-OHDA induced- α-synuclein-based models might useful nutritional therapy PD.

Language: Английский

Citations

14
Lipid mediated brain disorders: A perspective DOI
Anju Singh,

Samiksha Kukal,

Neha Kanojia

et al.

Prostaglandins & Other Lipid Mediators, Journal Year: 2023, Volume and Issue: 167, P. 106737 - 106737

Published: April 20, 2023

Language: Английский

Citations

13
Wild Mushrooms: A Hidden Treasure of Novel Bioactive Compounds DOI Creative Commons
Gebreselema Gebreyohannes, Desta Berhe Sbhatu

International Journal of Analytical Chemistry, Journal Year: 2023, Volume and Issue: 2023, P. 1 - 20

Published: Sept. 22, 2023

Secondary metabolites are hidden gems in mushrooms. Understanding these secondary metabolites' biological and pharmacological effects can be aided by identifying them. The purpose of this work was to profile the mycochemical components extracts Auricularia auricula judae, Microporus xanthopus, Termitomyces umkowaani, Trametes elegans, versicolor comprehend their capabilities. Mushroom samples were collected from Kenya's Arabuko-Sokoke Kakamega National Reserved Forests identified using morphological molecular techniques. Chloroform, 70% ethanol, hot water solvents used extract components. Gas chromatography mass spectrometry (GC-MS) analyze chloroform, all species examined. A total 51 compounds isolated classified as carboxylic acids, esters, phenols, fatty alcohol, epoxides, aldehydes, isoprenoid lipids, steroids. Tetracosamethyl-cyclododecasiloxane (18.90%), oleic acid (72.90%), phenol, 2, 6-bis (1, 1-dimethylethyl)-4-methyl-, methylcarbamate (26.56%) found high concentrations A. auricular M. T. versicolor, respectively. Fatty acids make up majority elegans chloroform umkowaani ethanol extract, Particularly, play crucial roles anti-inflammatory, hypocholesterolemic, anticancer, antibiofilm formation activities. These bioactive elements indicate that five wild mushrooms may reliable sources for therapeutic development. Therefore, additional research is required usefulness chemicals many functional areas improve present understanding macrofungi.

Language: Английский

Citations

11
The gut microbiome from middle-aged women with depression modulates depressive-like behaviors and plasma fatty acid metabolism in female middle-aged mice DOI
Huan Yu,

Wenmao Yang,

Yi-Huan Chen

et al.

Journal of Psychiatric Research, Journal Year: 2024, Volume and Issue: 173, P. 139 - 150

Published: March 21, 2024

Language: Английский

Citations

4
Improvement in the prediction power of an astrocyte genome-scale metabolic model using multi-omic data DOI Creative Commons

Andrea Angarita-Rodríguez,

Nicolás Mendoza-Mejía,

Janneth González

et al.

Frontiers in Systems Biology, Journal Year: 2025, Volume and Issue: 4

Published: Jan. 3, 2025

Introduction The availability of large-scale multi-omic data has revolution-ized the study cellular machinery, enabling a systematic understanding biological processes. However, integration these datasets into Genome-Scale Models Metabolism (GEMs) re-mains underexplored. Existing methods often link transcriptome and proteome independently to reaction boundaries, providing models with estimated maximum rates based on individual datasets. This independent approach, however, introduces uncertainties inaccuracies. Methods To address challenges, we applied principal component analysis (PCA)-based approach integrate data. method facilitates reconstruction context-specific grounded in multi-omics data, enhancing their relevance predictive capacity. Results Using this successfully reconstructed an astrocyte GEM improved prediction capabilities compared state-of-the-art available literature. Discussion These advancements underscore potential inte-gration refine metabolic modeling its critical role studying neurodegeneration developing effective therapies.

Language: Английский

Citations

0