《生命科学》 2025, 37(4): 384-392

蛋白质乳酸化修饰在阿尔茨海默病中的作用机制

左佰睿 , 王　珅 , 杨运杰 , 牟连伟^*

广州体育学院，广东省运动与健康重点实验室，广州 510500

摘　要：

乳酸化修饰是乳酸积累导致的对组蛋白和非组蛋白进行的翻译后修饰。乳酸在阿尔茨海默病(Alzheimer’s disease, AD) 脑内呈现出病程阶段和细胞类型的差异性变化。AD 的主要病理特征是大脑皮质和海马等脑区细胞外出现大量老年斑、神经元内现大量的神经纤维缠结(neurofibrillary tangles, NFTs) 以及小胶质细胞介导的神经炎症。β- 淀粉样蛋白前体蛋白(amyloid precursor protein, АPP) 在K612 位点乳酸化和组蛋白乳酸化均参与β- 淀粉样蛋白(amyloid β-protein, Aβ) 的产生和清除。Tau 蛋白和组蛋白乳酸化可调控tau 蛋白磷酸化和NFTs。AD 中组蛋白H3K18la 和H4K12la 调控小胶质细胞介导的神经炎症。该文概述了乳酸化修饰的研究进展，并深入剖析乳酸化修饰在AD 发病机制中的具体作用，特别是Aβ 代谢、tau 蛋白磷酸化和神经炎症。

通讯作者：牟连伟 , Email:bsumlw140243@126.com

The role and mechanism of lactylation in Alzheimer's disease

ZUO Bai-Rui , WANG Shen , YANG Yun-Jie , MU Lian-Wei^*

Guangdong Provincial Key Laboratory of Physical Activity and Health Promotion, Guangzhou Sport University, Guangzhou 510500, China

Abstract:

Lactylation is a post-translational modification that occurs in both histones and non-histone proteins due o the accumulation of lactate. Lactate in the brains of  Alzheimer's disease (AD) exhibits differential changes based on disease stage and cell type. AD disease is pathologically characterized by the extracellular accumulation of numerous senile plaques and the intracellular formation of abundant neurofibrillary tangles (NFTs) in brain regions, such as the cerebral cortex and hippocampus, along with microglial-mediated neuroinflammation. Amyloid precursor protein (APP) lysine 612 lactylation and histone lactylation are involved in the production and clearance of amyloid β-protein (Aβ). Tau and histone lactylation regulate tau protein phosphorylation and NFTs. Histone H3K18la and H4K12la regulate microglia-mediated neuroinflammation in AD. This article summarizes the research progress on lactylation and explores the specific roles of lactylation in the pathogenesis of AD, with particular emphasis on Aβ metabolism, tau phosphorylation, and  neuroinflammation.

Communication Author：MU Lian-Wei , Email:bsumlw140243@126.com