PROTEOMICS - CLINICAL APPLICATIONS, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 28, 2024
The hippocampus has long been associated with cognition and memory function, the implications of lysine lactylation (Kla), a recently identified post-translational modification (PTM), in role remain largely unexplored.
Language: Английский
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
Nature Communications, Journal Year: 2024, Volume and Issue: 15(1)
Published: Nov. 22, 2024
Glycolysis-derived lactate was identified as substrate for histone lactylation, which has been regarded a significant role in transcriptional regulation many tissues. However, the of lactylation metabolic center, hypothalamus, is still unknown. Here, we show that hypothalamic pro-opiomelanocortin (POMC) neuron-specific deletion family with sequence similarity 172, member A (Fam172a) can increase and protect mice against diet-induced obesity (DIO) related disorders. Conversely, overexpression Fam172a POMC neurons led to an obesity-like phenotype. Using RNA-seq CUT&Tag chromatin profiling analyzes, find knockdown activates glycolytic process increases peptidylglycine α-amidating monooxygenase (PAM), affects synthesis α-MSH, via H4K12la (histone lactylation). In addition, pharmacological inhibition production clearly abrogates anti-obesity effect PFKO (POMC-Cre, Fam172aloxP/loxP, knockout). These findings highlight importance development our results mainly concern male mice. reported play regulation. it's hypothalamus authors disorders
Language: Английский
Citations
5
Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13
Published: March 28, 2025
Lactate, as a metabolic product or energy substrate, participates in various neurological processes within the physiological and pathological frameworks of central nervous system (CNS). The groundbreaking application multi-omics integration technologies has unveiled novel role for lactate: lactylation, unique post-translational modification (PTM) that covalently attaches lactate groups to lysine residues on proteins. This process precisely regulates protein function gene expression, profoundly influencing progression diseases. lactylation is meticulously regulated by variety key enzymes pathways, forming dynamic intricate network. In this review, we summarize involved specifically "Writers," "Erasers," "Readers." Furthermore, systematically categorize observed cell types CNS investigate its multifaceted roles processes, including neurodegenerative diseases, brain tumors, injuries. By consolidating latest research findings field, our review aims highlight significance these discoveries future explore their potential translational applications.
Language: Английский
Citations
0
Cell Death Discovery, Journal Year: 2025, Volume and Issue: 11(1)
Published: April 30, 2025
Lactate, the end product of glycolysis, plays a crucial role in cellular signaling and metabolism. The discovery lactylation, novel post-translational modification, has uncovered lactate regulating diseases, especially brain. Lactylation connects genetic encoding with protein function, thereby influencing key biological processes. Increasing evidence supports lactate-mediated lactylation as critical modulator neurological disorders. This review offers an overview metabolism highlighting recent advances understanding regulatory enzymes their central nervous system. We investigate impact on brain dysfunctions, including neurodegenerative cerebrovascular disorders, neuroinflammation, tumors, psychiatric conditions. Moreover, we highlight therapeutic potential targeting treating disorders outline research gaps future directions needed to advance this promising field.
Language: Английский
Citations
0
Advanced Exercise and Health Science, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 1, 2024
Language: Английский
Citations
2
Experimental Neurology, Journal Year: 2024, Volume and Issue: 381, P. 114929 - 114929
Published: Aug. 22, 2024
Language: Английский
Citations
0
PROTEOMICS - CLINICAL APPLICATIONS, Journal Year: 2024, Volume and Issue: unknown
Published: Nov. 28, 2024
The hippocampus has long been associated with cognition and memory function, the implications of lysine lactylation (Kla), a recently identified post-translational modification (PTM), in role remain largely unexplored.
Language: Английский
Citations
0