OGDHL ameliorates cognitive impairment and Alzheimer's disease-like pathology via activating Wnt/β-catenin signaling in Alzheimer's disease mice

被引：6

作者：

Yao, Li ^{[1
]}

Xu, Xuemin ^{[1
]}

Xu, Yukun ^{[1
]}

Li, Chunyan ^{[2
]}

Xie, Fang ^{[3
]}

Guo, Minghao ^{[1
]}

Liu, Zhaoyang ^{[1
]}

Liu, Xiaoming ^{[1
]}

机构：

[1] Shandong Univ Tradit Chinese Med, Affiliated Hosp, Dept Geriatr Med, Jinan, Peoples R China

[2] Shizhong Dist Peoples Hosp Jinan, Dept Internal Med Tradit Chinese Med, Jinan, Peoples R China

[3] Shandong Univ Tradit Chinese Med, Sch Tradit Chinese Med, Jinan, Peoples R China

来源：

BEHAVIOURAL BRAIN RESEARCH | 2022年 / 418卷

关键词：

Alzheimer's disease; OGDHL; KGDHC; Cognitive deficits; Wnt/beta-catenin signaling; ALPHA-KETOGLUTARATE DEHYDROGENASE; OXIDATIVE STRESS; COMPLEX; PATHOGENESIS; BRAINS; MODEL;

D O I：

10.1016/j.bbr.2021.113673

中图分类号：

B84 [心理学]; C [社会科学总论]; Q98 [人类学];

学科分类号：

03 ; 0303 ; 030303 ; 04 ; 0402 ;

摘要：

Alzheimer's disease (AD) is one of the most common neurodegenerative diseases related to several types of pathophysiological signs, including beta-amyloid (A beta) plaque accumulation, neuroinflammation, and neurofibrillary tangles. Similar to one of the three subunits of alpha-ketoglutarate dehydrogenase complex (KGDHC), oxoglutarate dehydrogenase-like (OGDHL) appears to be downregulated in triple-transgenic Alzheimer's (3 x Tg-AD) mice. KGDHC activity is specifically reduced in the brains of people with AD. However, the underlying mechanism of OGDHL in the cause of AD is still unknown. Herein, we confirmed the low expression of OGDHL in the brain of 3 x Tg-AD based on real-time quantitative PCR, Western blot, and immunohistochemistry. We also found that the upregulation of OGDHL can reduce the memory deficits of 3 x Tg-AD mice, thereby reminding its nervous system neuroprotective effect in AD. Next, we confirmed that the increase in OGDHL could reduce neuroinflammation, amyloid plaque load, and tau phosphorylation in 3 x Tg-AD mice. Additionally, we showed that the overexpression of OGDHL could activate Wnt/beta-catenin signaling based on the expression of Wnt7B in vitro. Taken together, the results show that the rise of OGDHL reasonably improves the cognitive functions according to the activation of the Wnt/beta-catenin signaling pathway. Therefore, this enzyme may be a potential strategy for AD treatment.

引用

页数：11

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