Lactate metabolism and histone lactylation in the central nervous system disorders: impacts and molecular mechanisms DOI Creative Commons
Yao Wang, Ping Li, Yuan Xu

et al.

Journal of Neuroinflammation, Journal Year: 2024, Volume and Issue: 21(1)

Published: Nov. 28, 2024

Brain takes up approximately 20% of the total body oxygen and glucose consumption due to its relatively high energy demand. Glucose is one major sources generate ATP, process which can be realized via glycolysis, oxidative phosphorylation, pentose phosphate pathways others. Lactate serves as a hub molecule amid these metabolic pathways, it may function product substrate variety enzymes signal molecule. Thus, roles lactate in central nervous system (CNS) diseases need comprehensively elucidated. Histone lactylation novel lactate-dependent epigenetic modification that plays an important role immune regulation maintaining homeostasis. However, there's still lack studies unveiling functions histone CNS. In this review, we first reviewed CNS under both physiological pathological conditions. Subsequently, we've further discussed various neurological diseases. Furthermore, future perspectives regarding therapeutic potentials stroke are also elucidated, possess potential clinical applications.

Language: Английский

Anaerobic metabolism promotes breast cancer survival via Histone-3 Lysine-18 lactylation mediating PPARD axis DOI Creative Commons
Ying Xu,

Weiwei Meng,

Yingqi Dai

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 8, 2025

Abstract Histone lactylation plays a crucial role in cancer progression, but its impact on breast (BC) tumorigenesis is still unclear. We utilized chromatin immunoprecipitation sequencing with H3K18la antibodies, transcriptomics of clinical BC samples, and proteomics ATAC-seq analyses vivo tumors to identify the genes regulated by transcription factor PPARD. qPCR Western blot assays were used detect expressions molecules. discovered that levels higher tissues compared adjacent non-cancerous tissues. promoted expression PPARD, which turn influenced AKT, not ILK. analysis revealed glycolysis cells enhanced accessibility. Additionally, we confirmed HDAC2 HDAC3 act as “erasers” for H3 lysine lactylation. During analysis, AKT-phosphorylation aerobic respiration inhibitor group exhibited an apparent disparity activity. Our study demonstrated changes downstream PPARD support cell survival under anaerobic conditions. accelerated proliferation promoting phosphorylation AKT. This highlights therapeutic potential targeting H3K18la/PPARD/AKT axis cancer, providing new insights into epigenetic regulation metabolism (Trial registration: The was approved Research Ethics Committee Shandong Provincial Third Hospital (KYLL-2023057; https://www.medicalresearch.org.cn/ )).

Language: Английский

Citations

3
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

2
Lactate-induced protein lactylation in cancer: functions, biomarkers and immunotherapy strategies DOI Creative Commons
Wenjuan Wang, Hong Wang, Qi Wang

et al.

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

Published: Jan. 10, 2025

Lactate, long viewed as a byproduct of glycolysis and metabolic waste. Initially identified within the context yogurt fermentation, lactate's role extends beyond culinary applications to its significance in biochemical processes. Contemporary research reveals that lactate functions not merely terminal product but also nexus for initiating physiological pathological responses body. Lysine lactylation (Kla), novel post-translational modification (PTM) proteins, has emerged pivotal mechanism by which exerts regulatory influence. This epigenetic potential alter gene expression patterns, thereby impacting Increasing evidence indicates correlation between adverse prognosis various malignancies. Consequently, this review article aims encapsulate proteins interact with lactate, elucidate tumorigenesis progression, explore therapeutic targets afforded modulation lactylation. The objective is clarify oncogenic provide strategic framework future directions burgeoning field.

Language: Английский

Citations

1
Lactylation in cancer: metabolic mechanism and therapeutic strategies DOI Creative Commons
Ying Sui, Ziyang Shen, Zhenling Wang

et al.

Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)

Published: Feb. 20, 2025

Recent progress in cancer metabolism research has identified lactylation as a critical post-translational modification influencing tumor development and progression. The process relies on lactate accumulation the activation of lactate-sensitive acyltransferases. Beyond its role epigenetic regulation, emerged significant factor evolution, offering fresh opportunities for developing targeted therapies that transcend traditional approaches. This review explores growing importance biology highlights potential advancing diagnostic tools therapeutic strategies.

Language: Английский

Citations

1
Histone lactylation in macrophage biology and disease: from plasticity regulation to therapeutic implications DOI Creative Commons

Chuncha Bao,

Qing Ma, Xuchao Ying

et al.

EBioMedicine, Journal Year: 2024, Volume and Issue: 111, P. 105502 - 105502

Published: Dec. 10, 2024

Language: Английский

Citations

5
Metabolic cross-talk between glioblastoma and glioblastoma-associated microglia/macrophages: From basic insights to therapeutic strategies DOI
Yuan Gao, Mengxia Zhang, Guihua Wang

et al.

Critical Reviews in Oncology/Hematology, Journal Year: 2025, Volume and Issue: 208, P. 104649 - 104649

Published: Feb. 6, 2025

Language: Английский

Citations

0
Lactylation modification in cancer: mechanisms, functions, and therapeutic strategies DOI Creative Commons
Mengqi Lv,

Yefei Huang,

Yansu Chen

et al.

Experimental Hematology and Oncology, Journal Year: 2025, Volume and Issue: 14(1)

Published: March 8, 2025

Cancer remains the leading cause of mortality worldwide, and emergence drug resistance has made identification new therapeutic targets imperative. Lactate, traditionally viewed as a byproduct glycolysis with limited ATP-producing capacity, recently gained recognition critical signaling molecule. It plays key role not only in cancer cell metabolism but also shaping tumor microenvironment (TME). Histone lysine lactylation, newly identified post-translational modification, been shown to influence range cellular processes cancer. Current research focuses on mechanisms functions histone lactylation cancer, including its gene expression regulation, signal transduction, protein synthesis. However, despite these advancements, there are still plenty barriers quest unravel modification. The single-cell spatial transcriptomics may offer valuable insights for selecting targets. This review provides comprehensive summary applications modification clinical settings. Through detailed analysis, we identify challenges limitations that exist current landscape. These lay groundwork future studies by highlighting promising directions.

Language: Английский

Citations

0
Causal effect between circulating metabolic markers and glioma: a bidirectional, two-sample, Bayesian weighted Mendelian randomization DOI Creative Commons
Jiachen Wang,

C Wang,

Shenglan Li

et al.

Discover Oncology, Journal Year: 2025, Volume and Issue: 16(1)

Published: March 14, 2025

Glioma is the most common malignant tumor in central nervous system with significant challenges for its treatment and prognosis. Based on publicly available genome-wide association study data, this employed a bidirectional, two-sample Mendelian randomization (MR) analysis, combined Bayesian weighted MR, to investigate causal effect of 233 circulating metabolic traits glioma subtypes, expectation discovering new diagnostic therapeutic targets. The MR revealed that Total cholesterol total lipids ratio large VLDL Ratio polyunsaturated fatty acids (PUFAbyFA) are risk factors glioma, while free or phospholipids small HDL protective against glioma. IDL, ratios cholesteryl esters medium VLDL, as well linoleic acid (LA 18:2), phosphatidylcholine, sphingomyelins levels non-GBM Free identified factor results were robust sensitivity analyses mendelian randomization. effects metabolites explored through reverse provide potential biomarkers early diagnosis

Language: Английский

Citations

0
The lactylation modification of proteins plays a critical role in tumor progression DOI Creative Commons

Dai Yi,

Ke Zhou,

Yu Pan

et al.

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

Published: March 19, 2025

Lactylation modifications have been shown to be a novel type of protein post-translational (PTMs), providing new perspective for understanding the interaction between cellular metabolic reprogramming and epigenetic regulation. Studies that lactylation plays an important role in occurrence, development, angiogenesis, invasion metastasis tumors. It can not only regulate phenotypic expression functional polarization immune cells, but also participate formation tumor drug resistance through variety molecular mechanisms. In this review, we review latest research progress modification tumors, focusing on its mechanism action cell regulation microenvironment (TME), resistance, aiming provide theoretical basis ideas discovery therapeutic targets methods. Through in-depth analysis modification, it is expected open up direction treatment potential strategies overcoming improving clinical efficacy.

Language: Английский

Citations

0
Lactylation in Glioblastoma: A Novel Epigenetic Modifier Bridging Epigenetic Plasticity and Metabolic Reprogramming DOI Open Access

Qingya Qiu,

Hui Deng,

Ping Song

et al.

International Journal of Molecular Sciences, Journal Year: 2025, Volume and Issue: 26(7), P. 3368 - 3368

Published: April 4, 2025

Glioblastoma, the most common and aggressive primary malignant brain tumor, is characterized by a high rate of recurrence, disability, lethality. Therefore, there pressing need to develop more effective prognostic biomarkers treatment approaches for glioblastoma. Lactylation, an emerging form protein post-translational modification, has been closely associated with lactate, metabolite glycolysis. Since initial identification lactylation sites in core histones 2019, accumulating evidence shown critical role that plays glioblastoma development, assessment poor clinical prognosis, immunosuppression, which provides fresh angle investigating connection between metabolic reprogramming epigenetic plasticity cells. The objective this paper present overview roles expanding field research explore practical value developing novel plans combining targeted therapy immunotherapy.

Language: Английский

Citations

0