European Journal of Medicinal Chemistry, Journal Year: 2025, Volume and Issue: 295, P. 117790 - 117790
Published: May 20, 2025
Language: Английский
Journal of Translational Medicine, Journal Year: 2024, Volume and Issue: 22(1)
Published: Jan. 10, 2024
As more is learned about lactate, it acts as both a product and substrate functions shuttle system between different cell populations to provide the energy for sustaining tumor growth proliferation. Recent discoveries of protein lactylation modification mediated by lactate play an increasingly significant role in human health (e.g., neural osteogenic differentiation maturation) diseases tumors, fibrosis inflammation, etc.). These views are critically first described detail this review. Hence, here, we focused on new target, lactylation, which may be "double-edged sword" diseases. The main purpose review was describe how multiple physiological pathological processes their potential mechanisms through in-depth summary preclinical vitro vivo studies. Our work aims ideas treating accelerate translation from bench bedside.
Language: Английский
Citations
20
Theranostics, Journal Year: 2024, Volume and Issue: 14(11), P. 4297 - 4317
Published: Jan. 1, 2024
Aim:Although lactate supplementation at the reperfusion stage of ischemic stroke has been shown to offer neuroprotection, whether role accumulated ischemia phase is neuroprotection or not remains largely unknown.Thus, in this study, we aimed investigate roles and mechanisms brain regulating injury stroke.Methods Results: Pharmacological inhibition production by either inhibiting LDHA glycolysis markedly attenuated mouse stroke.In contrast, additional supplement further aggravates injury, which may be closely related induction neuronal death A1 astrocytes.The contributing increased promotive formation protein lysine lactylation (Kla), while post-treatment did influence Kla levels with neuroprotection.Increased were found mainly neurons HPLC-MS/MS analysis immunofluorescent staining.Then, pharmacological blocking shuttle showed decreased brains.Additionally, Ldha specific knockout astrocytes (Aldh1l1 CreERT2 ; fl/fl mice, cKO) mice MCAO constructed results that level was accompanied a decrease volume cerebral infarction cKO compared control groups.Furthermore, writer p300 its antagonist A-485 significantly alleviates glial activation reduction level, resulting extending window improving functional recovery for stroke.Conclusion: Collectively, derived from promoting formation, suggesting presents new therapeutic targets treatment stroke.
Language: Английский
Citations
19
Biochemical Pharmacology, Journal Year: 2024, Volume and Issue: 225, P. 116331 - 116331
Published: May 29, 2024
Language: Английский
Citations
14
Biological reviews/Biological reviews of the Cambridge Philosophical Society, Journal Year: 2024, Volume and Issue: unknown
Published: Sept. 16, 2024
ABSTRACT In recent years, a significant breakthrough has emerged in biology, the identification of lactylation, novel post‐translational process. This intriguing modification is not limited to specific class proteins but occurs across diverse range, including histones, signalling molecules, enzymes, and substrates. It can exert broad regulatory role various diseases, ranging from developmental anomalies neurodegenerative disorders inflammation cancer. Thus, it presents exciting opportunities for exploring innovative treatment approaches. As result, there been surge research interest, leading deeper understanding molecular mechanisms functions underlying lactylation within physiological pathological processes. Here, we review detection biological disease effects, providing systematic overview this modification.
Language: Английский
Citations
12
Frontiers in Immunology, Journal Year: 2024, Volume and Issue: 14
Published: Jan. 9, 2024
Osteoarthritis (OA) has been a leading cause of disability in the elderly and there remains lack effective therapeutic approaches as mechanisms pathogenesis progression have yet to be elucidated. As OA progresses, cellular metabolic profiles energy production are altered, emerging reprogramming highlights importance specific pathways disease progression. crucial part glucose metabolism, glycolysis bridges inflammatory dysfunctions. Moreover, glycolytic pathway is involved different areas metabolism inflammation, associated with variety transcription factors. To date, it not fully elucidated whether changes its key enzymes onset or OA. This review summarizes important role mediating inducing tissue inflammation injury, aim providing further insights into pathological functions proposing new targets for treatment
Language: Английский
Citations
11
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
Experimental Cell Research, Journal Year: 2024, Volume and Issue: 440(2), P. 114135 - 114135
Published: June 18, 2024
Language: Английский
Citations
7
Communications Biology, Journal Year: 2024, Volume and Issue: 7(1)
Published: Dec. 26, 2024
Acute ischemic stroke (AIS) triggers immune responses and neuroinflammation, contributing to brain injury. Histone lactylation, a metabolic stress-related histone modification, plays critical role in various diseases, but its involvement cerebral ischemia remains unclear. This study utilized transient middle artery occlusion/reperfusion (MCAO/R) model an oxygen–glucose deprivation/reoxygenation (OGD/R) investigate the of microglial lactylation ischemia–reperfusion Lactate overload post-AIS increased while reduced SMEK1 expression microglia correlated with elevated lactate neuroinflammation. Microglia-specific deficiency enhanced production by inhibiting pyruvate dehydrogenase kinase 3-pyruvate (PDK3-PDH) pathway, increasing H3 lysine 9 (H3K9la), activating Ldha Hif-1α transcription, promoting glycolysis. overexpression improved neurological recovery mice. highlights as novel regulator potential therapeutic target for mitigating neuroinflammation enhancing after AIS. identifies
Language: Английский
Citations
6
Neuroreport, Journal Year: 2024, Volume and Issue: 35(14), P. 895 - 903
Published: July 24, 2024
Ischemic stroke remains a major cause of disability and mortality. Nuclear receptor coactivator 4 (NCOA4)-mediated ferritinophagy is involved in cerebral ischemic injury. Additionally, lactylation regulates the progression ischemia This study aimed to investigate impact NCOA4 on glycolysis hippocampal neuron cells its modification. Middle artery occlusion (MCAO) mouse oxygen-glucose deprivation (OGD)-treated HT22 cell models were generated. Ferritinophagy was evaluated via detecting ferrous iron (Fe 2+ ), glutathione, malondialdehyde, protein levels. Glycolysis assessed by examining glucose consumption, lactate production, extracellular acidification rate. The using immunoprecipitation immunoblotting. Brain injury vivo analyzed measuring brain infarct neurological function. results showed that expression increased blood patients with acute stroke, peri-infarct region MCAO mice (increased percentage: 142.11%) OGD-treated 114.70%). Knockdown inhibited induced OGD. Moreover, OGD promoted at lysine (K)450 sites, which enhanced stability. interfering attenuated infarction dysfunction mice. Lactylation K450 sites promotes cells, thereby accelerating These findings suggest novel pathogenesis stroke.
Language: Английский
Citations
5
Molecular Medicine, Journal Year: 2024, Volume and Issue: 30(1)
Published: Aug. 31, 2024
Language: Английский
Citations
5