Mechanism of reduced muscle atrophy via ketone body (D)-3-hydroxybutyrate

Cell & Bioscience, Journal Year: 2022, Volume and Issue: 12(1)

Published: June 20, 2022

Muscle atrophy is an increasingly global health problem affecting millions, there a lack of clinical drugs or effective therapy. Excessive loss muscle mass the typical characteristic atrophy, manifesting as weakness accompanied by impaired metabolism protein and nucleotide. (D)-3-hydroxybutyrate (3HB), one main components ketone body, has been reported to be for obvious hemodynamic effects in atrophic cardiomyocytes exerts beneficial metabolic reprogramming healthy muscle. This study aims exploit how 3HB therapeutic treating induced hindlimb unloaded mice.Anabolism/catabolism balance was maintained with via Akt/FoxO3a mTOR/4E-BP1 pathways; homeostasis regulation includes pathways ubiquitin-proteasomal, autophagic-lysosomal, responses unfolded-proteins, heat shock anti-oxidation. Metabolomic analysis revealed effect decreased purine degradation reduced uric acid atrophied muscles; enhanced utilization from glutamine glutamate also provides evidence promotion during synthesis proteins nucleotides.3HB significantly inhibits weights, myofiber sizes diameters mouse model; it facilitates positive nucleotides accumulation wasting muscles, revealing effectiveness atrophy.

Language: Английский

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Review: myogenic and muscle toxicity targets of environmental methylmercury exposure

Archives of Toxicology, Journal Year: 2024, Volume and Issue: 98(6), P. 1645 - 1658

Published: March 28, 2024

Language: Английский

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ALS and Parkinson's disease genes CHCHD10 and CHCHD2 modify synaptic transcriptomes in human iPSC-derived motor neurons

Neurobiology of Disease, Journal Year: 2020, Volume and Issue: 141, P. 104940 - 104940

Published: May 11, 2020

Mitochondrial intermembrane space proteins CHCHD2 and CHCHD10 have roles in motor neuron diseases such as amyotrophic lateral sclerosis, spinal muscular atrophy axonal neuropathy Parkinson's disease. They form a complex of unknown function. Here we address the importance these two human neurons. We show that gene edited induced pluripotent stem cells (iPSC) lacking either or are viable can be differentiated into functional neurons fire spontaneous evoked action potentials. Mitochondria knockout iPSC sustain ultrastructure but increased proton leakage respiration, reciprocal compensatory increases CHCHD10. Knockout largely overlapping transcriptome profiles compared to isogenic control line, particular for synaptic expression. Our results absence alters mitochondrial respiration neurons, inducing similar responses. Thus, pathogenic mechanisms may involve loss function resulting from defective energy metabolism.

Language: Английский

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κ‑opioid receptor agonist, U50488H, inhibits pyroptosis through NLRP3 via the Ca²⁺/CaMKII/CREB signaling pathway and improves synaptic plasticity in APP/PS1 mice

Molecular Medicine Reports, Journal Year: 2021, Volume and Issue: 24(1)

Published: May 25, 2021

Alzheimer's disease (AD) is a progressive neurodegenerative brain disorder with slow onset in most cases. Clinically, dementia associated AD characterized by memory disorders, aphasia, executive dysfunction and personality behavior changes. Currently, treatment strategies attempt to reduce certain symptoms, however there no cure for AD. The aim of the present study was identify novel strategy Thus, protective effects κ‑opioid receptor (KOR) agonist, U50488H on neural damage mice were investigated. underlying mechanism Ca²⁺/calcium/calmodulin‑dependent protein kinase II/cyclic adenosine monophosphate‑response element binding (Ca²⁺/CaMKII/CREB) signaling pathway evaluated. Amyloid precursor (APP)/presenilin‑1 (PS1) treated subcutaneously KOR agonist 28 days. learning abilities APP/PS1 evaluated using Morris water maze test. Damage hippocampal neurons assessed hematoxylin eosin staining. Inflammatory factors injury markers detected ELISA. Neurons examined immunofluorescence dendritic spines observed Golgi‑Cox Western blotting used detect NOD‑, LRR‑ pyrin domain‑containing 3, microglial ptosis Ca²⁺/CaMKII/CREB‑related pathway. significantly improved mice, inhibited microglia pyroptosis synaptic plasticity which reversed antagonist. symptoms inhibiting Ca²⁺/CaMKII/CREB

Language: Английский

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Epigenetic mapping of the somatotropic axis in Nile tilapia reveals differential DNA hydroxymethylation marks associated with growth

Genomics, Journal Year: 2021, Volume and Issue: 113(5), P. 2953 - 2964

Published: June 30, 2021

In vertebrates, the somatotropic axis comprising pituitary gland, liver and muscle plays a major role in myogenesis.Its output terms of growth is highly affected by nutritional environmental cues, thus likely epigenetically regulated.Hydroxymethylation emerging as DNA modification that modulates gene expression but holistic characterization hydroxymethylome has not been investigated to date.Using reduced representation 5-hydroxymethylcytosine profiling we demonstrate tissuespecific localization 5-hydroxymethylcytosines at single nucleotide resolution.Their abundance within bodies promoters several growth-related genes supports their pertinent regulation.We propose cytosine hydroxymethylation may contribute phenotypic plasticity through epigenetic regulation axis.

Language: Английский

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Pathway-based metabolomics study of sarcopenia-related traits in two US cohorts

Aging, Journal Year: 2022, Volume and Issue: 14(5), P. 2101 - 2112

Published: March 2, 2022

We aimed to validate two metabolites, aspartic acid and glutamic acid, which were associated with sarcopenia-related traits, muscle mass strength, in our previous untargeted metabolomics study identify novel metabolites from five metabolic pathways involving these metabolites. included a discovery cohort of 136 white women aged 20-40 years (used for the analysis) validation 174 subjects ≥ 60 years, including men black. A targeted LC-MS assay successfully detected 12 important pathways. Aspartic was strength cohort, but not cohort. However, sarcopenia traits both cohorts. Additionally, N-acetyl-L-aspartic carnosine newly identified that cohorts, respectively. did observe any significant sex race differences associations Our findings indicated might be consistently across age, sex, race. They also suggested age-specific involved regulation.

Language: Английский

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In vivo Evaluation of a Newly Synthesized Acetylcholinesterase Inhibitor in a Transgenic Drosophila Model of Alzheimer’s Disease

Frontiers in Neuroscience, Journal Year: 2021, Volume and Issue: 15

Published: June 30, 2021

Alzheimer’s disease is a neurodegenerative characterized by disrupted memory, learning functions, reduced life expectancy, and locomotor dysfunction, as result of the accumulation aggregation amyloid peptides that cause neuronal damage in circuits. In current study, we exploited transgenic Drosophila melanogaster line, expressing amyloid-β to investigate efficacy newly synthesized acetylcholinesterase inhibitor, named XJP-1, potential AD therapy. Behavioral assays confocal microscopy were used characterize drug effect on symptomatology peptide deposition. The induced this particular model recapitulates scenario observed human patients, showing shortened lifespan along with significant plaques brain. XJP-1 treatment resulted improvement symptoms reduction diminishing rate. comparison clinically effective drugs, our results demonstrated has similar effects symptomatology, but at 10 times lower concentration than donepezil. It also showed an earlier beneficial days after treatment, for donepezil 20 days, while other drugs tested have no such effect. As novel potent AChE study demonstrates inhibition enzyme improves amyloid-induced , reducing number within fruit fly CNS. Thus, compound therapeutic be further investigated AD.

Language: Английский

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Metazoan evolution and diversity of glutamate receptors and their auxiliary subunits

Neuropharmacology, Journal Year: 2021, Volume and Issue: 195, P. 108640 - 108640

Published: June 8, 2021

Language: Английский

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Human skeletal muscle ageing atlas

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2022, Volume and Issue: unknown

Published: May 25, 2022

Abstract Skeletal muscle ageing increases the incidence of age-associated frailty and sarcopenia in elderly worldwide, leading to increased morbidity mortality. However, our understanding cellular molecular mechanisms is still far from complete. Here, we generate a single-cell single-nucleus transcriptomic atlas skeletal 15 donors across adult human lifespan, accompanied by myofiber typing using imaging. Our reveals acting different compartments muscle, including stem cells (MuSCs), myofibers microenvironment. Firstly, uncover two driving MuSC ageing, namely decrease ribosome biogenesis an increase inflammation. Secondly, identify set nuclei populations explaining preferential degeneration fast-twitch suggest compensate for their loss. Importantly, neuromuscular junction accessory population, which helps aged-related denervation. Thirdly, reveal multiple microenvironment cell types contributing inflammatory milieu producing cytokines chemokines attract immune cells. Finally, provide comparable mouse further investigate conserved specific hallmarks species. In summary, present comprehensive resource combining data modalities, significantly expands biology ageing.

Language: Английский

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Long non‐coding RNA CASC15 enhances learning and memory in mice by promoting synaptic plasticity in hippocampal neurons

Exploration, Journal Year: 2024, Volume and Issue: 4(6)

Published: March 28, 2024

Abstract Alzheimer's disease (AD) is a debilitating systemic disorder that has detrimental impact on the overall well‐being of individuals. Emerging research suggests long non‐coding RNAs play role in neural development and function. Nevertheless, precise relationship between lncRNAs remains uncertain. The authors' recent discoveries have uncovered an unconventional mechanism involving regulation synaptic plasticity functioning hippocampal fragile X mental retardation protein 1 (FMR1)—neurotrophin 3 (NTF3) pathway, which mediated by cancer susceptibility candidate 15 ( CASC15 ). Subsequently, functional rescue experiments were performed to illustrate efficient delivery exosomes harboring significant amount 2610307p16Rik transcripts, murine equivalent human , region mice. This resulted improvements morphological cognitive function APP/PS1 Given pivotal involvement distinctive regulatory mechanisms CASC15‐FMR1‐NTF3 axis, emerges as promising biomarker for may even possess potential feasible therapeutic target.

Language: Английский

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