Low-Dose Radiation Induces Alterations in Fatty Acid and Tyrosine Metabolism in the Mouse Hippocampus: Insights from Integrated Multiomics DOI Creative Commons

Rekha Koravadi Narasimhamurthy,

Babu Santhi Venkidesh,

Sampara Vasishta

et al.

ACS Chemical Neuroscience, Journal Year: 2024, Volume and Issue: 15(18), P. 3311 - 3320

Published: Aug. 26, 2024

In recent years, there has been a drastic surge in neurological disorders with sporadic cases contributing more than ever to their cause. Radiation exposure through diagnostic or therapeutic routes often results injuries that may lead neurodegenerative pathogenesis. However, the underlying mechanisms regulating impact of near-low doses ionizing radiation are not known. particular, changes caused by metabolomic reprogramming have yet elucidated. Hence, present study, C57BL/6 mice were exposed single whole-body X-ray dose 0.5 Gy, and 14 days post-treatment, hippocampus was subjected analysis. The irradiated animals showed significant alterations 15 metabolites, which aligned altered tyrosine, phenylalanine, alpha-linolenic acid metabolism biosynthesis unsaturated fatty acids. Furthermore, multiomics interaction network comprising metabolomics RNA sequencing data analysis provided insights into gene-metabolite interactions. Tyrosine revealed be most altered, demonstrated several crucial genes metabolites. study regulation low-dose radiation-induced neurotoxicity at level its implications for pathogenesis disorders. also provides novel pathways following near-low-dose IR link diseases such as Alzheimer's disease Parkinson's disease.

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

25
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

7
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

7
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

6
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

13
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
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

11
Leptin as a potential neuroprotective target in Parkinson’s Disease: Exploring its role in Neuroinflammation, oxidative Stress, and dopaminergic neurodegeneration DOI

Vipul Sharma,

Bhat Zada Unjum Saqib,

Khadga Raj Aran

et al.

Neuroscience, Journal Year: 2025, Volume and Issue: unknown

Published: March 1, 2025

Language: Английский

Citations

0
Del Río Hortega’s insights into oligodendrocytes: recent advances in subtype characterization and functional roles in axonal support and disease DOI Creative Commons
Eneritz López-Muguruza,

Carla Peiró-Moreno,

Fernando Pérez‐Cerdá

et al.

Frontiers in Neuroanatomy, Journal Year: 2025, Volume and Issue: 19

Published: March 12, 2025

Pío Del Río Hortega (1882–1945) was a giant of modern neuroscience and perhaps the most impactful member Cajal’s School. His contributions to clarifying structure nervous system were key understanding brain beyond neurons. He uncovered microglia oligodendrocytes, latter until then named mesoglia. Most importantly, characterization oligodendroglia subtypes he made has stood omics revolution that added molecular details relevant comprehend their biological properties. Astounding as it may seem on today’s eyes, postulated century ago oligodendrocytes provide trophic support axons, an idea is now doubt under scrutiny dysfunction at axon-myelin unit neurodegeneration. Here, we revised recent advancements in oligodendrocyte biology shed light Hortega’s ideas ago.

Language: Английский

Citations

0