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阿尔茨海默病中晚期糖基化终末产物受体分子成像的研究进展

Progress of RAGE Molecular Imaging in Alzheimer's Disease.

作者信息

Kong Yanyan, Liu Cuiping, Zhou Yinping, Qi Jingxuan, Zhang Chencheng, Sun Bomin, Wang Jiao, Guan Yihui

机构信息

PET Center, Huashan Hospital, Fudan University, Shanghai, China.

Laboratory of Molecular Neural Biology, School of Life Sciences, Shanghai University, Shanghai, China.

出版信息

Front Aging Neurosci. 2020 Aug 4;12:227. doi: 10.3389/fnagi.2020.00227. eCollection 2020.

Abstract

Alzheimer's disease (AD) is a progressive neurodegenerative disease characterized by senile plaques (SPs), which are caused by amyloid beta (Aβ) deposition and neurofibrillary tangles (NFTs) of abnormal hyperphosphorylated tau protein. The receptor for advanced glycation end products (RAGE) binds to advanced glycation end products deposited during vascular dysfunction. Alzheimer's disease may occur when RAGE binds to Aβ and releases reactive oxygen species, further exacerbating Aβ deposition and eventually leading to SPs and NFTs. As it is involved in early AD, RAGE may be considered as a more potent biomarker than Aβ. Positron emission tomography provides valuable information regarding the underlying pathological processes of AD many years before the appearance of clinical symptoms. Thus, to further reveal the role of RAGE in AD pathology and for early diagnosis of AD, a tracer that targets RAGE is needed. In this review, we first describe the early diagnosis of AD and then summarize the interaction between RAGE and Aβ and Tau that is required to induce AD pathology, and finally focus on RAGE-targeting probes, highlighting the potential of RAGE to be used as an effective target. The development of RAGE probes is expected to aid in AD diagnosis and treatment.

摘要

阿尔茨海默病(AD)是一种进行性神经退行性疾病,其特征为老年斑(SPs),老年斑由淀粉样β蛋白(Aβ)沉积和异常高磷酸化tau蛋白的神经原纤维缠结(NFTs)引起。晚期糖基化终末产物受体(RAGE)与血管功能障碍期间沉积的晚期糖基化终末产物结合。当RAGE与Aβ结合并释放活性氧时,可能会发生阿尔茨海默病,这会进一步加剧Aβ沉积,并最终导致老年斑和神经原纤维缠结。由于RAGE参与早期AD,它可能被认为是比Aβ更有效的生物标志物。正电子发射断层扫描在临床症状出现前许多年就能提供有关AD潜在病理过程的有价值信息。因此,为了进一步揭示RAGE在AD病理中的作用并实现AD的早期诊断,需要一种靶向RAGE的示踪剂。在这篇综述中,我们首先描述AD的早期诊断,然后总结RAGE与Aβ和Tau之间诱导AD病理所需的相互作用,最后聚焦于靶向RAGE的探针,突出RAGE作为有效靶点的潜力。RAGE探针的开发有望有助于AD的诊断和治疗。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/9c69/7417350/43d60cc3e6ef/fnagi-12-00227-g001.jpg

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