Hai Shuangshuang, Hou Yadan, Zhang Meiyan, Gao Xiaoyan, Yang Tuo, Shang Xiuli, Sun Xiaohong
Department of Geriatrics, The Fourth Affiliated Hospital of China Medical University, Shenyang, Liaoning 110032, China.
Department of Neurology, Chifeng Municipal Hospital, Chifeng, Inner Mongolia 024000, China.
Aging Dis. 2025 Jun 25. doi: 10.14336/AD.2025.0338.
Alzheimer's disease (AD) is a neurodegenerative disorder primarily characterized by cognitive decline; however, its pathogenesis remains incompletely understood. In recent years, the role of lactate metabolism and its derived lactylation modifications in AD has received increasing attention. As a product of glycolysis, lactate is not only a key molecule in energy metabolism but also regulates gene expression and protein function through lactylation modifications. Studies have shown that in the brains of AD patients, glucose metabolism is significantly reduced, while glycolysis is upregulated, and lactate levels are elevated. Nevertheless, the research regarding the relationship between lactylation and AD remains limited. Building on recent advances in understanding lactylation in neurodegenerative diseases and related conditions, we analyze and explore the potential relationships between lactylation and AD from the perspectives of β-amyloid (Aβ) deposition, tau protein pathology, and neuroinflammation. In summary, lactylation, as a novel post-translational modification holds significant promise in elucidating the pathological mechanisms and advancing the treatment of AD. A deeper investigation into its molecular mechanisms and regulatory networks may open new avenues for the diagnosis and treatment of AD.
阿尔茨海默病（AD）是一种主要以认知功能衰退为特征的神经退行性疾病；然而，其发病机制仍未完全明确。近年来，乳酸代谢及其衍生的乳酰化修饰在AD中的作用受到了越来越多的关注。作为糖酵解的产物，乳酸不仅是能量代谢中的关键分子，还通过乳酰化修饰调节基因表达和蛋白质功能。研究表明，在AD患者的大脑中，葡萄糖代谢显著降低，而糖酵解上调，乳酸水平升高。然而，关于乳酰化与AD之间关系的研究仍然有限。基于近年来在神经退行性疾病及相关病症中对乳酰化认识的进展，我们从β-淀粉样蛋白（Aβ）沉积、tau蛋白病理学和神经炎症等角度分析并探讨乳酰化与AD之间的潜在关系。总之，乳酰化作为一种新型的翻译后修饰，在阐明AD的病理机制和推动其治疗方面具有巨大潜力。对其分子机制和调控网络进行更深入的研究可能为AD的诊断和治疗开辟新途径。
