Lactylation Modification in Cardio-cerebral Diseases: A State-of-the-art Review DOI
Zihan Liao, Bei Chen, Tong Yang

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102631 - 102631

Published: Dec. 1, 2024

Language: Английский

Non-histone lactylation: unveiling its functional significance DOI Creative Commons
Peng Shi, Yongjie Ma, Shangzhe Zhang

et al.

Frontiers in Cell and Developmental Biology, Journal Year: 2025, Volume and Issue: 13

Published: Jan. 24, 2025

Lactylation, a newly discovered protein posttranslational modification (PTM) in 2019, primarily occurs on lysine residues. Lactylation of histones was initially identified, and subsequent studies have increasingly demonstrated its widespread presence non-histone proteins. Recently, high-throughput proteomics identified large number lactylated proteins sites, revealing their global regulatory role disease development. Notably, this is catalyzed by lactyltransferase reversed delactylase, with numerous new enzymes, such as AARS1/2, reported to be involved. Specifically, these revealed how lactylation exerts influence through alterations spatial conformation, molecular interactions, enzyme activity subcellular localization. Indeed, implicated various physiological pathological processes, including tumor development, cardiovascular cerebrovascular diseases, immune cell activation psychiatric disorders. This review provides the latest advancements research roles lactylation, highlighting crucial scientific importance for future studies.

Language: Английский

Citations

2
Lactylation in CNS disorders: mechanisms, cellular function, and disease relevance DOI Creative Commons

Jiaxin Tian,

Tongyu Zhang, Ruidan Zhang

et al.

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
Anti-Alzheimer effects of an HDAC6 inhibitor, WY118, alone and in combination of lithium chloride: Synergistic suppression of ferroptosis via the modulation of tau phosphorylation and MAPK signaling DOI

Zhonghui Lu,

Zixing Jiang,

Xiaoling Huang

et al.

European Journal of Pharmacology, Journal Year: 2025, Volume and Issue: unknown, P. 177605 - 177605

Published: April 1, 2025

Language: Английский

Citations

0
The role of protein lactylation in brain health and disease: current advances and future directions DOI Creative Commons

M.E. Han,

Wenfeng He, Wengen Zhu

et al.

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
Ferroptosis and Iron Homeostasis: Molecular Mechanisms and Neurodegenerative Disease Implications DOI Creative Commons
Nurzhan Abdukarimov, Kamilya Kokabi, Jeannette Kunz

et al.

Antioxidants, Journal Year: 2025, Volume and Issue: 14(5), P. 527 - 527

Published: April 28, 2025

Iron dysregulation has emerged as a pivotal factor in neurodegenerative pathologies, especially through its capacity to promote ferroptosis, unique form of regulated cell death driven by iron-catalyzed lipid peroxidation. This review synthesizes current evidence on the molecular underpinnings focusing how disruptions iron homeostasis interact with key antioxidant defenses, such system Xc−-glutathione-GPX4 axis, tip neurons toward lethal oxidative damage. Building these mechanistic foundations, we explore ferroptosis intersects hallmark pathologies Alzheimer’s disease (AD) and Parkinson’s (PD) examine accumulation vulnerable brain regions may fuel disease-specific protein aggregation neurodegeneration. We further surveyed distinct components highlighting role peroxidation enzymes, mitochondrial dysfunction, recently discovered parallel pathways that either exacerbate or mitigate neuronal death. Finally, discuss insights open new avenues for neuroprotective strategies, including chelation inhibitors. By questions, this seeks clarify state knowledge proposes directions harness modulation intervention.

Language: Английский

Citations

0
NFE2L1 as a central regulator of proteostasis in neurodegenerative diseases: interplay with autophagy, ferroptosis, and the proteasome DOI Creative Commons
Hossein Khodadadi,

Kamila Łuczyńska,

Dawid Winiarczyk

et al.

Frontiers in Molecular Neuroscience, Journal Year: 2025, Volume and Issue: 18

Published: May 1, 2025

Maintaining proteostasis is critical for neuronal health, with its disruption underpinning the progression of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Huntington's diseases. Nuclear Factor Erythroid 2-Related 1 (NFE2L1) has emerged a key regulator proteostasis, integrating proteasome function, autophagy, ferroptosis to counteract oxidative stress protein misfolding. This review synthesizes current knowledge on role NFE2L1 in maintaining homeostasis, focusing mechanisms mitigating proteotoxic supporting cellular offering protection against neurodegeneration. Furthermore, we discuss pathological implications dysfunction explore potential therapeutic target. By highlighting gaps understanding presenting future research directions, this aims elucidate NFE2L1's advancing treatment strategies

Language: Английский

Citations

0
Lactylation as a metabolic epigenetic modification: Mechanistic insights and regulatory pathways from cells to organs and diseases DOI
Cong Chen, Jie Wang, Xueying Zhu

et al.

Metabolism, Journal Year: 2025, Volume and Issue: unknown, P. 156289 - 156289

Published: May 1, 2025

Language: Английский

Citations

0
NSUN2 lactylation drives cancer cell resistance to ferroptosis through enhancing GCLC-dependent glutathione synthesis DOI Creative Commons
Kaifeng Niu, Zixiang Chen, Mengge Li

et al.

Redox Biology, Journal Year: 2024, Volume and Issue: 79, P. 103479 - 103479

Published: Dec. 20, 2024

Language: Английский

Citations

3
Lactylation Modification in Cardio-cerebral Diseases: A State-of-the-art Review DOI
Zihan Liao, Bei Chen, Tong Yang

et al.

Ageing Research Reviews, Journal Year: 2024, Volume and Issue: unknown, P. 102631 - 102631

Published: Dec. 1, 2024

Language: Английский

Citations

1