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

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

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Fatty Acids: A Safe Tool for Improving Neurodevelopmental Alterations in Down Syndrome?

Nutrients, Journal Year: 2022, Volume and Issue: 14(14), P. 2880 - 2880

Published: July 13, 2022

The triplication of chromosome 21 causes Down syndrome (DS), a genetic disorder that is characterized by intellectual disability (ID). ID start in utero, leading to impairments neurogenesis, and continue into infancy, dendritogenesis, spinogenesis, connectivity. These defects are associated with alterations mitochondrial metabolic functions precocious aging, the early development Alzheimer’s disease. Intense efforts currently underway, taking advantage DS mouse models discover pharmacotherapies for neurodevelopmental cognitive deficits DS. Many treatments proved effective may raise safety concerns over human use, especially at life stages. Accumulating evidence shows fatty acids, which nutrients present normal diets, exert numerous positive effects on brain. Here, we review (i) knowledge obtained from animal regarding acids brain, focusing particularly prominent DS, (ii) progress recently made model, suggesting indeed represent useful treatment This scenario should prompt scientific community further explore potential benefit people

Language: Английский

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Metabolic Regulations of Smilax china L. against β-Amyloid Toxicity in Caenorhabditis elegans

Metabolites, Journal Year: 2024, Volume and Issue: 14(1), P. 49 - 49

Published: Jan. 13, 2024

Smilax china L. (Chinaroot) is a natural herb that has multiple uses, such as being used to make tea and food. Both its roots leaves have different uses due their unique components. In this study, we analyzed the extract of S. china. using LC-HRMS evaluated neuroprotective effects metabolic regulation on Caenorhabditis elegans. Chinaroot prolonged life span healthy nematodes, delayed paralysis time transgenic CL4176, reduced level β-amyloid deposition in CL2006. The comprehensive analysis metabolomics qRT-PCR revealed exerted through valine, leucine isoleucine degradation fatty acid pathways. Moreover, first discovered expressions T09B4.8, ech-7, agxt-1 were linked Chinaroot. material by modulating abnormalities AD model C. Our study provides new foundation for development functional food properties functions.

Language: Английский

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Increased molar ratio of free fatty acids to albumin in blood as cause and early biomarker for the development of cataracts and Alzheimer's disease

Experimental Eye Research, Journal Year: 2024, Volume and Issue: 243, P. 109888 - 109888

Published: April 6, 2024

Cataracts and Alzheimer's disease (AD) are closely linked associated with aging systemic diseases that increase the molar ratio of free fatty acids to albumin (mFAR) in blood. From results our earlier studies on development senile cataracts from recently published literature pathogenesis disease, we suggest there is a common lipotoxic cascade for both diseases, explaining strong connection between aging, an elevated mFAR blood, cataract formation, AD. Long-chain (FFA) transported blood as FFA/albumin complexes. In young people, vascular barriers eyes brain, very similar their structure effect, reduce complex concentration around 650 μmol/l 1-3 aqueous humour well cerebrospinal fluid brain. At such low concentrations acid uptake target cells - lens epithelial brain rises increasing concentrations, especially when load molecules mFAR>1. higher instance plasma or interstitial tissue spaces, becomes increasingly independent mainly function (Richieri et al., 1993). normally below 1.0. people over 40 years old, increases by decreasing enhancing FFA. The association C6-unsaturated FFA risk factors (Hennig 1984). Damage barrier fluid, leading mitochondrial dysfunction death cells, cataracts, An age-dependent has been found 177 patients, correlating mitochondria-mediated apoptotic opacification (Iwig 2004). Mitochondrial also early crucial event pathology, connected generation amyloid beta peptides (Leuner 2012). Very recently, production confirmed lenses causing (Moncaster 2022). view this, propose formation AD, initiated and/or mFAR>1

Language: Английский

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

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

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