Lactylation and Central Nervous System Diseases DOI Creative Commons
Ye Chen, Dongqiong Xiao, Xihong Li

et al.

Brain Sciences, Journal Year: 2025, Volume and Issue: 15(3), P. 294 - 294

Published: March 11, 2025

As the final product of glycolysis, lactate serves as an energy substrate, metabolite, and signaling molecule in various diseases mediates lactylation, epigenetic modification that occurs under both physiological pathological conditions. Lactylation is a crucial mechanism by which exerts its functions, participating vital biological activities such glycolysis-related cellular macrophage polarization, nervous system regulation. links metabolic regulation to central (CNS) diseases, traumatic brain injury, Alzheimer’s disease, acute ischemic stroke, schizophrenia, revealing diverse functions lactylation CNS. In future, further exploration lactylation-associated enzymes proteins needed develop specific inhibitors or activators, could provide new tools strategies for treatment CNS diseases.

Language: Английский

Lactylation in health and disease: physiological or pathological? DOI Creative Commons
Lijun Zhao,

Haonan Qi,

Huiying Lv

et al.

Theranostics, Journal Year: 2025, Volume and Issue: 15(5), P. 1787 - 1821

Published: Jan. 2, 2025

Lactate is an indispensable substance in various cellular physiological functions and plays regulatory roles different aspects of energy metabolism signal transduction. Lactylation (Kla), a key pathway through which lactate exerts its functions, has been identified as novel posttranslational modification (PTM). Research indicates that Kla essential balancing mechanism variety organisms involved many biological processes pathways. closely related to disease development represents potential important new drug target. In line with existing reports, we searched for newly discovered sites on histone nonhistone proteins; reviewed the mechanisms (particularly focusing enzymes directly reversible regulation Kla, including "writers" (modifying enzymes), "readers" (modification-binding "erasers" (demodifying enzymes); summarized crosstalk between PTMs help researchers better understand widespread distribution diverse functions. Furthermore, considering "double-edged sword" role both pathological contexts, this review highlights "beneficial" states (energy metabolism, inflammatory responses, cell fate determination, development, etc.) "detrimental" pathogenic or inducive effects processes, particularly malignant tumors complex nontumor diseases. We also clarify molecular health disease, discuss feasibility therapeutic Finally, describe detection technologies their applications diagnosis clinical settings, aiming provide insights treatment diseases accelerate translation from laboratory research practice.

Language: Английский

Citations

0

Electroacupuncture Pretreatment Reduces Ischemic Brain Injury by Inhibiting the Lactate Production and Its Derived Protein Lactylation Formation DOI Creative Commons

Xinru Pan,

Yao‐Dan Zhang,

Yehua Gan

et al.

CNS Neuroscience & Therapeutics, Journal Year: 2025, Volume and Issue: 31(1)

Published: Jan. 1, 2025

ABSTRACT Aim Given that electroacupuncture (EA) pretreatment inhibits lactate production and lactate‐derived lysine lactation (Kla) aggravates ischemic brain injury, we aimed to investigate whether the formation of Kla protein is involved in EA alleviate injury. Methods was performed on Baihui acupoint (GV20) male C57BL/6J mice before receiving permanent middle cerebral artery occlusion (pMCAO) surgery. Western blot immunofluorescent staining were used observe neuronal survival, astrocyte activation, levels, levels brains assayed with a commercial kit. TTC neurological function scores are evaluate damage mice. Results We found increased content significantly decreased tissue after pretreatment, accompanied by reduction activation injury death. Meantime, effective reversing worsening caused supplementation. However, did not further reduce ameliorate stroke inhibition glycolysis. Conclusion Our study reveals reduced inhibiting its derived stroke.

Language: Английский

Citations

0

Protocol for investigating astrocytic mitochondria in neurons of adult mice using two-photon microscopy DOI

Jian Zhou,

Fengling Du, Fan Zhang

et al.

STAR Protocols, Journal Year: 2025, Volume and Issue: 6(1), P. 103600 - 103600

Published: Jan. 25, 2025

Language: Английский

Citations

0

The impact of glycolysis on ischemic stroke: from molecular mechanisms to clinical applications DOI Creative Commons
Yingquan Liu,

Peijia Hu,

Hongliang Cheng

et al.

Frontiers in Neurology, Journal Year: 2025, Volume and Issue: 16

Published: Jan. 24, 2025

Ischemic stroke (IS), a leading cause of disability and mortality worldwide, remains significant challenge due to its complex pathogenesis. Glycolysis, central metabolic pathway, plays critical role in bridging the gap between dysfunction neurological impairment. During ischemic conditions, glycolysis replaces oxidative phosphorylation as primary energy source for brain tissue. However, ischemia–reperfusion state, neuronal cells show particular reliance on aerobic glycolysis. Immune cells, such monocytes, also contribute atheromatous plaque formation thrombi through increased Given glycolysis’s involvement various pathological stages IS, it offers potential improved diagnosis, treatment, prevention. This review comprehensively explores different phases addresses existing controversies, discusses diagnostic therapeutic applications. By elucidating intricate relationship this aims provide novel insights future research clinical advancements.

Language: Английский

Citations

0

Lactylation: The Metabolic Accomplice Shaping Cancer's Response to Radiotherapy and Immunotherapy DOI
Danqing Yu, Qingping Zhong, Yanlin Wang

et al.

Ageing Research Reviews, Journal Year: 2025, Volume and Issue: unknown, P. 102670 - 102670

Published: Jan. 1, 2025

Language: Английский

Citations

0

Proteomic analysis of whole blood to investigate the therapeutic effects of nervonic acid on cerebral ischemia-reperfusion injury in rats DOI Creative Commons
Qingqing Li,

Fengrong Zhang,

Xianyu Li

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 28, 2025

Introduction Blood proteomics offers a powerful approach for identifying disease-specific biomarkers. However, no reliable blood markers are currently available the diagnosis stroke. Nervonic acid (NA), vital long-chain monounsaturated fatty found in mammalian nervous tissue, shows promising therapeutic potential neurological disorders. This study aimed to develop methodology whole identify early warning biomarkers and evaluate drug treatment efficacy. Methods After modeling via classic thread embolization method, samples were collected from rats. Morphological assessments of brain tissue indicated that NA significantly mitigated neuronal damage The differential protein expression profile was analyzed using Liquid Chromatography—Tandem Mass Spectrometry (LC-MS/MS) proteomics. Results ZZZGene Ontology (GO) analysis revealed that, compared ginkgo biloba extract (EGb), proteins differentially expressed under intervention predominantly involved oxidative stress response calcium-dependent adhesion processes. Key targets middle cerebral artery occlusion (MCAO) models included ENO1, STAT3, NME2, VCL, CCT3. Discussion proteomic provides comprehensive understanding profiles associated with disease states, offering valuable insights into enabling evaluation EGb Our findings underscore protective effects against ischemia-reperfusion injury highlight its as

Language: Английский

Citations

0

Identification of M4 muscarinic acetylcholine receptor expressing astrocytes that regulate locomotion and survival in murine prion disease DOI Open Access
Gonzalo S. Tejeda, Colin Molloy, Carrie K. Jones

et al.

bioRxiv (Cold Spring Harbor Laboratory), Journal Year: 2025, Volume and Issue: unknown

Published: Jan. 29, 2025

Abstract Whilst there has been much focus on the function of neuronally expressed members muscarinic acetylcholine receptor family (mAChR) less attention paid to expression profile and role five this (M 1 -M 5 mAChRs) in non-neuronal cells brain. Using genetically engineered mice we identify a previously unappreciated sub-population astrocytes expressing M 4 mAChR subtype. These are located various brain regions that include brainstem, hypothalamus and, most abundantly, cerebellum. Signalling proteomic analysis positive from cerebellum established functional subtype its regulation protein expression. Genetic ablation revealed specific locomotion behaviour. Importantly, context murine prion disease, model terminal neurodegeneration associated with profound neuroinflammation, observed significant expansion report experiments astrocyte detrimental effect late-stage disease. Together provide evidence play normal neurophysiology progression inflammatory neurodegenerative

Language: Английский

Citations

0

The role of lactylation in tumor growth and cancer progression DOI Creative Commons

Khulood Al-Malsi,

Sinan Xie, Yunshi Cai

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 15

Published: Feb. 4, 2025

Background Lactate’s perception of lactate has changed over the last 30 years from a straightforward metabolic byproduct to complex chemical with important biological activities, such as signal transduction, gluconeogenesis, and mitochondrial respiration. In addition its contributions, far-reaching repercussions. This review highlights role in course cancer by highlighting lactylation unique epigenetic alteration. The purpose this is clarify functions biology tumors, particular focus on translational potential pathways diagnosis treatment approaches. Methods summarizes research relationship between cancer, an emphasis histone lactylation, effect gene expression, influence tumor microenvironment. By establishing connection byproducts regulation, we investigated how affects immune inflammation, cellular repair. Findings Histone or lysine residues proteins, increases transcriptional activity facilitates expression genes involved homeostasis These findings have implications for treatment. Lactylation, example, activates Arg1, which hallmark M2 macrophage phenotype implicated immunosuppression growth. ability dynamically alter further supported function deacetylase(HDAC)inhibitor impact acetylation. Its wide-ranging involvement metabolism control been demonstrated discovery sites histones various cell types, including cells.

Language: Английский

Citations

0

Higher mitochondrial protein-Succinylation detected in lung tissues of idiopathic pulmonary fibrosis patients DOI

Yunmulan Zhao,

Wenyu Hou,

Liqing Yang

et al.

Journal of Proteomics, Journal Year: 2025, Volume and Issue: 314, P. 105400 - 105400

Published: Feb. 10, 2025

Language: Английский

Citations

0

GLA deficiency causes cardiac hypertrophy via enhanced autophagy DOI

Wei Ou,

Xi Li,

Kuo Tang

et al.

Science China Life Sciences, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 17, 2025

Language: Английский

Citations

0