醇脱氢酶
发病机制
疾病
阿尔茨海默病
医学
神经科学
酒
生物化学
化学
生物
免疫学
内科学
作者
Zuting Ye,Yanming Liu,Xingjiang Jin,Yiqing Wu,Hang Zhao,Tingting Gao,Qiangfeng Deng,Jianhua Cheng,Lin Jia,Zhiqian Tong
标识
DOI:10.1016/j.ijbiomac.2024.130580
摘要
Although Alzheimer's disease (AD) characterized with senile plaques and neurofibrillary tangles has been found for over 100 years, its molecular mechanisms are ambiguous. More worsely, the developed medicines targeting amyloid-beta (Aβ) and/or tau hyperphosphorylation did not approach the clinical expectations in patients with moderate or severe AD until now. This review unveils the role of a vicious cycle between Aβ-derived formaldehyde (FA) and FA-induced Aβ aggregation in the onset course of AD. Document evidence has shown that Aβ can bind with alcohol dehydrogenase (ADH) to form the complex of Aβ/ADH (ABAD) and result in the generation of reactive oxygen species (ROS) and aldehydes including malondialdehyde, hydroxynonenal and FA; in turn, ROS-derived H2O2 and FA promotes Aβ self-aggregation; subsequently, this vicious cycle accelerates neuron death and AD occurrence. Especially, FA can directly induce neuron death by stimulating ROS generation and tau hyper hyperphosphorylation, and impair memory by inhibiting NMDA-receptor. Recently, some new therapeutical methods including inhibition of ABAD activity by small molecules/synthetic polypeptides, degradation of FA by phototherapy or FA scavengers, have been developed and achieved positive effects in AD transgenic models. Thus, breaking the vicious loop may be promising interventions for halting AD progression.
科研通智能强力驱动
Strongly Powered by AbleSci AI