Imaging sigma receptors in the brain: New opportunities for diagnosis of Alzheimer’s disease and therapeutic development
Imaging sigma receptors in the brain: New opportunities for diagnosis of Alzheimer’s disease and therapeutic development
复制标题
大脑中西格玛受体成像：阿尔茨海默病诊断和治疗开发的新机遇
DOI：
10.1016/j.neulet.2018.07.033
复制
发表时间：
2019-01
影响因子：
2.5
通讯作者：
Yiyun Huang
中科院分区：
文献类型：
--
作者：
Hongmei Jia;Ying Zhang;Yiyun Huang
Sigma-1(σ-1)受体是位于内质网线粒体相关膜上的伴侣蛋白，而Sigma-2受体(σ-2)是内质网驻留的膜蛋白。最近的证据表明，这两种受体在阿尔茨海默病(AD)的病理生理学中都扮演着重要的角色，因此是开发新的、改变疾病的治疗策略的靶点。正电子发射断层成像(PET)等基于放射性配基的分子成像技术是研究活体蛋白质靶点表达和功能的有力工具。在这篇综述中，我们综述了针对σ-1或σ-2受体的PET放射性配体的发展，并评估了它们在人类成像应用中的潜力。利用σ1或σ2受体特异性放射性配基在人体内进行正电子发射计算机断层扫描成像，可以在活体内研究这些受体，并进一步了解它们在AD发病和进展中各自的作用。此外，正电子发射计算机断层成像可用于靶点占位研究，以评估靶点定位，并与目前临床试验中的σ1受体激动剂和σ2受体拮抗剂的受体占位和治疗反应相关联。σ-1和σ-2受体在脑内的神经成像有望为AD的病理生理机制提供新的线索，并可能为AD的诊断和新的AD治疗策略的疗效监测提供新的生物标志物。
The sigma-1 (σ1) receptor is a chaperone protein located on the mitochondria-associated membrane of the endoplasmic reticulum, while the sigma-2 receptor (σ2) is an endoplasmic reticulum-resident membrane protein. Recent evidence indicates that both of these receptors figure prominently in the pathophysiology of Alzheimer’s disease (AD) and thus are targets for the development of novel, disease-modifying therapeutic strategies. Radioligand-based molecular imaging technique such as positron emission tomography (PET) imaging is a powerful tool for the investigation of protein target expression and function in living subjects. In this review, we survey the development of PET radioligands for the σ1or σ2receptors and assess their potential for human imaging applications. The availability of PET imaging with σ1or σ2receptor-specific radioligands in humans will allow the investigation of these receptorsin vivoand lead to further understanding of their respective roles in AD pathogenesis and progression. Moreover, PET imaging can be used in target occupancy studies to assess target engagement and correlate receptor occupancy and therapeutic response of σ1receptor agonists and σ2receptor antagonists currently in clinical trials. It is expected that neuroimaging of σ1and σ2receptors in the brain will shed new light on AD pathophysiology and may provide us with new biomarkers for diagnosis of AD and efficacy monitoring of emerging AD therapeutic strategies.
登录
查看更多内容
影响因子：
3.7
作者：
Tadokoro S;Kanahara N;Kikuchi S;Hashimoto K;Masaomi I
通讯作者：
Masaomi I
F-18 标记的吲哚类似物作为高选择性放射性配体，用于大脑中 sigma-2 受体的成像
影响因子：
3.5
作者：
Wang Liang;Ye Jiajun;He Yingfang;Deuther-Conrad Winnie;Zhang Jinming;Zhang Xiaojun;Cui Mengchao;Steinbach Joerg;Huang Yiyun;Brust Peter;Jia Hongmei
通讯作者：
Jia Hongmei
影响因子：
3.1
作者：
K. Ishiwata;K. Kawamura;Tadayuki Kobayashi;K. Matsuno
通讯作者：
K. Ishiwata;K. Kawamura;Tadayuki Kobayashi;K. Matsuno
S2RSLDB：Sigma-2受体选择性配体的全面手动策划的，可访问的Internet可访问数据库。
影响因子：
8.6
作者：
Nastasi G;Miceli C;Pittalà V;Modica MN;Prezzavento O;Romeo G;Rescifina A;Marrazzo A;Amata E
通讯作者：
Amata E
σ2受体：一种用于癌症成像和治疗的新型蛋白质。
影响因子：
7.3
作者：
Mach, Robert H.;Zeng, Chenbo;Hawkins, William G.
通讯作者：
Hawkins, William G.