The roles of lactate and the interplay with m6A modification in diseases DOI Creative Commons

Fajuan Tang,

Dongqiong Xiao, Xihong Li

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Dec. 2, 2024

Lactate exhibits various biological functions, including the mediation of histone and non-histone lactylation to regulate gene transcription, influencing activity T lymphocytes, NK cells, macrophages in immune suppression, activating G protein-coupled receptor 81 for signal transduction, serving as an energy substrate. The m6A modification represents most prevalent post-transcriptional epigenetic alteration. It is regulated by m6A-related regulatory enzymes (including methyltransferases, demethylases, recognition proteins) that control splicing, stability, translation downstream target RNAs. Lactate-mediated at H3K18 can modulate modifications enhancing transcriptional expression levels enzymes. These play a crucial role progression diseases such cancer, fibrosis (in both liver lung), myocardial ischemia, cerebral hemorrhage, sepsis. Furthermore, are also subject lactate. In turn, these influence key glycolytic pathway or modify lactate transporter MCT4 via alterations impact subsequently affect processes.

Language: Английский

Insight into the roles of lactylation in macrophages: functions and clinical implications DOI

Min Shu,

Dingci Lu,

Ziyi Zhu

et al.

Clinical Science, Journal Year: 2025, Volume and Issue: 139(02), P. 151 - 169

Published: Jan. 1, 2025

Lactylation, a post-translational modification, has been linked to gene transcription regulation through epigenetic modulation in various pathophysiological processes. The lactylation regulatory proteins, known as writers, erasers, and readers, govern their dynamics by adding, removing, recognizing lactyl groups on proteins. Macrophages, cells of the immune system, maintain homeostasis, responding dynamically diverse internal external stimuli. Emerging researches unveil that lactylation, inducing macrophage activation polarization, affects functionality pathological conditions such inflammation, tumor microenvironment, fibrosis. Evidence progressively indicates lactate-driven alterations levels within macrophages can influence pathogenesis numerous diseases. This review aims systematically summarize research progress macrophages, explore its functions mechanisms which contributes pathology different disease phenotypes, propose future directions along with potential diagnostic therapeutic strategies.

Language: Английский

Citations

1
Role of TAK-242-Induced Histone Lactylation in Modulating Repair Macrophage Transformation in Ulcerative Colitis DOI
Chenfei Zhang, Xiaoling Huang

Immunological Investigations, Journal Year: 2025, Volume and Issue: unknown, P. 1 - 19

Published: Feb. 17, 2025

Background Ulcerative Colitis (UC) is a condition that causes ulceration and inflammation of the intestinal epithelium. UC treatment depends on macrophages' phenotypic switch from pro-inflammatory (M1) to anti-inflammatory tissue-repairing (M2). It has been reported epigenetic alteration histone lactylation affects macrophage activity phenotype. TAK-242, TLR4 inhibitor, stimulates generate reparative M2 macrophages.

Language: Английский

Citations

0
Impact of lactate on immune cell function in the tumor microenvironment: mechanisms and therapeutic perspectives DOI Creative Commons

Xuan-Yu Gu,

Jiali Yang, Rui Lai

et al.

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

Published: March 26, 2025

Lactate has emerged as a key regulator in the tumor microenvironment (TME), influencing both progression and immune dynamics. As byproduct of aerobic glycolysis, lactate satisfies metabolic needs proliferating cells while reshaping TME to facilitate evasion. Elevated levels inhibit effector such CD8 + T natural killer cells, supporting immunosuppressive regulatory myeloid-derived suppressor thus fostering an environment. promotes epigenetic reprogramming, stabilizes hypoxia-inducible factor-1α, activates nuclear factor kappa B, leading further immunological dysfunction. In this review, we examined role suppression, treatment resistance. We also discuss promising therapeutic strategies targeting metabolism, including dehydrogenase inhibitors, monocarboxylate transporter neutralization methods, all which can restore function enhance immunotherapy outcomes. By highlighting recent advances, review provides theoretical foundation for integrating lactate-targeted therapies into clinical practice. highlight potential synergy between these current immunotherapeutic strategies, providing new avenues addressing TME-related challenges improving outcomes patients with cancer.

Language: Английский

Citations

0
Characterization of lactylation-based phenotypes and molecular biomarkers in sepsis-associated acute respiratory distress syndrome DOI Creative Commons
Yiheng Wang, Wei An,

Zixuan Su

et al.

Scientific Reports, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 22, 2025

Language: Английский

Citations

0
Smart biomimetic “nano-med-fireman” blocking inflammation and lactate metabolism crosstalk for normalized spatiotemporal photo-immunotherapy DOI

Honglin Huang,

Ningxi Li, Zeng Li

et al.

Bioactive Materials, Journal Year: 2025, Volume and Issue: 51, P. 431 - 449

Published: May 21, 2025

Language: Английский

Citations

0
Metabolic Dysfunction in Parkinson’s Disease: Unraveling the Glucose–Lipid Connection DOI Creative Commons
Jeswinder Sian‐Hülsmann, Peter Riederer, Tanja Maria Michel

et al.

Biomedicines, Journal Year: 2024, Volume and Issue: 12(12), P. 2841 - 2841

Published: Dec. 13, 2024

Despite many years of research into the complex neurobiology Parkinson’s disease, precise aetiology cannot be pinpointed down to one causative agent but rather a multitude mechanisms. Current treatment options can alleviate symptomsbut only slightly slow progression and not cure disease its underlying causes. Factors that play role in causing debilitating neurodegenerative psycho-motoric symptoms include genetic alterations, oxidative stress, neuroinflammation, general inflammation, neurotoxins, iron toxicity, environmental influences, mitochondrial dysfunction. Recent findings suggest characteristic abnormal protein aggregation alpha-synuclein destruction substantia nigra neurons might due dysfunction related disturbances lipid glucose metabolism along with insulin resistance. The latter mechanism action mediated by receptor substrate docking proteins are involved neuronal survival signaling cell destruction. increased risk developing Type 2 Diabetes Mellitus endorses connection between metabolic neurodegeneration. Here, we explore highlight potential glycolipid cellular insults pathophysiology disorder, opening up new promising avenues for PD. Thus, antidiabetic drugs may employed as neuromodulators hinder disorder.

Language: Английский

Citations

3
Cracking Lysine Crotonylation (Kcr): Enlightening a Promising Post‐Translational Modification DOI Creative Commons

Marinda Westerveld,

Kosta Besermenji,

David Aidukas

et al.

ChemBioChem, Journal Year: 2024, Volume and Issue: unknown

Published: Oct. 27, 2024

Abstract Lysine crotonylation (Kcr) is a recently discovered post‐translational modification (PTM). Both histone and non‐histone Kcr‐proteins have been associated with numerous diseases including cancer, acute kidney injury, HIV latency, cardiovascular disease. Histone Kcr enhances gene expression to larger extend than the extensively studied lysine acetylation (Kac), suggesting as novel potential therapeutic target. Although scientific reports on were published in last years, relevant knowledge gaps concerning this PTM its regulation still remain. To date, only few selective Kcr‐interacting proteins identified methods for enrichment of chemical proteomics analysis are lacking. The development new techniques study underexplored could then clarify function health disease hopefully accelerate therapeutics Kcr‐related Herein we briefly review what known about mechanisms current used identify their interacting partners. This report aims highlight significant target existing that research must address.

Language: Английский

Citations

0
The roles of lactate and the interplay with m6A modification in diseases DOI Creative Commons

Fajuan Tang,

Dongqiong Xiao, Xihong Li

et al.

Cell Biology and Toxicology, Journal Year: 2024, Volume and Issue: 40(1)

Published: Dec. 2, 2024

Lactate exhibits various biological functions, including the mediation of histone and non-histone lactylation to regulate gene transcription, influencing activity T lymphocytes, NK cells, macrophages in immune suppression, activating G protein-coupled receptor 81 for signal transduction, serving as an energy substrate. The m6A modification represents most prevalent post-transcriptional epigenetic alteration. It is regulated by m6A-related regulatory enzymes (including methyltransferases, demethylases, recognition proteins) that control splicing, stability, translation downstream target RNAs. Lactate-mediated at H3K18 can modulate modifications enhancing transcriptional expression levels enzymes. These play a crucial role progression diseases such cancer, fibrosis (in both liver lung), myocardial ischemia, cerebral hemorrhage, sepsis. Furthermore, are also subject lactate. In turn, these influence key glycolytic pathway or modify lactate transporter MCT4 via alterations impact subsequently affect processes.

Language: Английский

Citations

0