Weng Yifei, Xie Guomin
Department of Neurology, The Affiliated People's Hospital of Ningbo University, No.251 East Baizhang Road, Ningbo, 315040, Zhejiang, China.
Department of Neurology, The Affiliated Lihuili Hospital of Ningbo University, No.57 Xingning Road, Ningbo, 315040, Zhejiang, China.
Biochem Genet. 2024 Dec 26. doi: 10.1007/s10528-024-11004-z.
Alzheimer's disease (AD) and mild cognitive impairment (MCI) are a serious global public health problem. The aim of this study was to analyze the key molecular pathological mechanisms that occur in early AD progression as well as MCI. Expression profiling data from brain homogenates of 8 normal volunteers, and 6 patients with prodromal AD who had developed MCI were analyzed, and the data were obtained from GSE12685. Further, overexpression of GABBR2 was achieved in human neuroblastoma cell lines SH-SY5Y and BE(2)-M17 using expression plasmid transfection. GABBR2 was significantly overexpressed in brain tissues of patients with prodromal AD who had developed MCI, as compared to normal brains. Moreover, GABBR2 overexpressing cells showed a significant increase in intracellular Ca concentration, a large amount of reactive oxygen species production, a large opening of the mitochondrial permeability transition pore and a significant increase in apoptosis compared with control cells. GABBR2 overexpression was significantly involved in early AD progression and MCI by causing cellular events such as intracellular Ca imbalance, oxidative stress, and mitochondrial dysfunction.
阿尔茨海默病（AD）和轻度认知障碍（MCI）是一个严重的全球公共卫生问题。本研究的目的是分析在AD早期进展以及MCI过程中发生的关键分子病理机制。对8名正常志愿者和6名已发展为MCI的前驱AD患者的脑匀浆表达谱数据进行了分析，数据来自GSE12685。此外，使用表达质粒转染在人神经母细胞瘤细胞系SH-SY5Y和BE(2)-M17中实现了GABBR2的过表达。与正常大脑相比，已发展为MCI的前驱AD患者的脑组织中GABBR2显著过表达。此外，与对照细胞相比，过表达GABBR2的细胞内Ca浓度显著增加，产生活性氧的量增加，线粒体通透性转换孔大量开放，细胞凋亡显著增加。GABBR2过表达通过引起细胞内Ca失衡、氧化应激和线粒体功能障碍等细胞事件，显著参与了AD早期进展和MCI。
