Lactate and Lactylation in the Brain: Current Progress and Perspectives

Li, Ruobing; Yang, Yi; Wang, Haoyu; Zhang, Tingting; Duan, Fangfang; Wu, Kaidi; Yang, Siyu; Xu, Ke; Jiang, Xicheng; Sun, Xiaowei

doi:10.1007/s10571-023-01335-7

Cited by 22 publications

(7 citation statements)

References 132 publications

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“…This, in turn, prevents the production of lactate and the modification of histones by lactylation, which further prevents macrophages from adopting the M2 phenotype linked to tissue repair [ 59 ]. Consequently, BCAP functions as an upstream bridging factor for aerobic glycolysis, facilitating the generation of lactate and stimulating lactylation of relevant histones produced by repair genes, thus contributing to the reduction of inflammation[ 60 ]. Notably, H3K18la levels in peripheral blood mononuclear (PBMC) from septic shock patients and histone lactylation in tumor-associated macrophages correlate positively with Arg1 transcript levels [ 16 , 61 ], although recent research challenges the direct causal relationship between lactylation and Arg1 expression.…”

Section: Protein Lactylation In Pathological Processesmentioning

confidence: 99%

Lactylation: the novel histone modification influence on gene expression, protein function, and disease

Hu,

He,

et al. 2024

Clin Epigenet

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Lactic acid, traditionally considered as a metabolic waste product arising from glycolysis, has undergone a resurgence in scientific interest since the discovery of the Warburg effect in tumor cells. Numerous studies have proved that lactic acid could promote angiogenesis and impair the function of immune cells within tumor microenvironments. Nevertheless, the precise molecular mechanisms governing these biological functions remain inadequately understood. Recently, lactic acid has been found to induce a posttranslational modification, lactylation, that may offer insight into lactic acid's non-metabolic functions. Notably, the posttranslational modification of proteins by lactylation has emerged as a crucial mechanism by which lactate regulates cellular processes. This article provides an overview of the discovery of lactate acidification, outlines the potential “writers” and “erasers” responsible for protein lactylation, presents an overview of protein lactylation patterns across different organisms, and discusses the diverse physiological roles of lactylation. Besides, the article highlights the latest research progress concerning the regulatory functions of protein lactylation in pathological processes and underscores its scientific significance for future investigations.

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Section: Protein Lactylation In Pathological Processesmentioning

confidence: 99%

Lactylation: the novel histone modification influence on gene expression, protein function, and disease

Hu,

He,

et al. 2024

Clin Epigenet

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“…PCr measurement provides an information on energy processes taking place in the local microenvironment of brain tissues and allows for the assessment of mitochondrial function in vivo [89]. In turn, lactate is usually considered as a product of glycolysis in hypoxic conditions, although it may also be a by-product of aerobic glycolysis in cancer cells [90][91][92]. Research in recent years also indicates the role of lactate, especially l-lactate, in improving memory, increasing cerebral blood flow, improving cerebral energy metabolism and stimulating the nervous system to regenerate [42,93].…”

Section: Correlation Analysis Of Lactates Glutamic Acid and Cortisol ...mentioning

confidence: 99%

Association of Blood Metabolomics Biomarkers with Brain Metabolites and Patient-Reported Outcomes as a New Approach in Individualized Diagnosis of Schizophrenia

Krzyściak,

Bystrowska,

Karcz

et al. 2024

IJMS

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Given its polygenic nature, there is a need for a personalized approach to schizophrenia. The aim of the study was to select laboratory biomarkers from blood, brain imaging, and clinical assessment, with an emphasis on patients’ self-report questionnaires. Metabolomics studies of serum samples from 51 patients and 45 healthy volunteers, based on the liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS/MS), led to the identification of 3 biochemical indicators (cortisol, glutamate, lactate) of schizophrenia. These metabolites were sequentially correlated with laboratory tests results, imaging results, and clinical assessment outcomes, including patient self-report outcomes. The hierarchical cluster analysis on the principal components (HCPC) was performed to identify the most homogeneous clinical groups. Significant correlations were noted between blood lactates and 11 clinical and 10 neuroimaging parameters. The increase in lactate and cortisol were significantly associated with a decrease in immunological parameters, especially with the level of reactive lymphocytes. The strongest correlations with the level of blood lactate and cortisol were demonstrated by brain glutamate, N-acetylaspartate and the concentrations of glutamate and glutamine, creatine and phosphocreatine in the prefrontal cortex. Metabolomics studies and the search for associations with brain parameters and self-reported outcomes may provide new diagnostic evidence to specific schizophrenia phenotypes.

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“…Normally, lactic acid is produced during glycolysis via pyruvate reduction; however, abnormal mitochondrial function and/or lactic acid clearance can disrupt lactic acid homeostasis, thereby affecting physiological brain functions [14][15][16][17]. Numerous studies report a prominent role for lactate in regulating brain function, providing energy fuel for neurons, and cellular signaling [16][17][18][19][20]. However, alterations in lactate homeostasis can result in neurological dysfunction and further the development of neuropsychiatric disorders [17][18][19]21].…”

Section: Alterations In Glucose Metabolismmentioning

confidence: 99%

Correlations of Blood and Brain NMR Metabolomics with Alzheimer’s Disease Mouse Models

Cheng,

Knörnschild,

Zhang

et al. 2024

Preprint

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Alzheimer’s disease (AD) is a complex, progressive neurodegenerative disorder, impacting millions of geriatric patients globally. Unfortunately, AD can only be diagnosed post-mortem, through analysis of autopsied brain tissue in human patients. This renders early detection and countering disease progression difficult. As AD progresses, the metabolomic profile of the brain and other organs can change. These alterations can be detected in peripheral systems (i.e., blood) such that biomarkers of the disease can be identified and monitored with minimal invasion. In this work, High-Resolution Magic Angle Spinning (HRMAS) Nuclear Magnetic Resonance (NMR) spectroscopy is used to correlate biochemical changes in mouse brain tissues, from the cortex and hippocampus to blood plasma. 10 µg of each brain tissue and 10 µL of blood plasma were obtained from 5XFAD Tg AD mice models (n=15, 8 female, 7 male) and female C57/BL6 wild-type mice (n=8). 51 spectral regions-of-interest (ROI) were identified, and 121 potential metabolites were assigned using the Human Metabolome Database and tabulated according to their trends (increase/decrease, false discovery rate significance). This work identified several metabolites that impact glucose oxidation (lactic acid, pyruvate, glucose-6-phosphate), allude to oxidative stress resulting in brain dysfuncton(L-cysteine, galactitol, propionic acid), as well as those interacting with other neural pathways (taurine, dimethylamine). This work also suggests correlated metabolomic changes within blood plasma, proposing an avenue for biomarker detection, ideally leading to improved patient diagnosis and prognosis in the future.

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Lactate and Lactylation in the Brain: Current Progress and Perspectives

Cited by 22 publications

References 132 publications

Lactylation: the novel histone modification influence on gene expression, protein function, and disease

Lactylation: the novel histone modification influence on gene expression, protein function, and disease

Association of Blood Metabolomics Biomarkers with Brain Metabolites and Patient-Reported Outcomes as a New Approach in Individualized Diagnosis of Schizophrenia

Correlations of Blood and Brain NMR Metabolomics with Alzheimer’s Disease Mouse Models

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