In vitro and in vivo assessment of novel derivatives for detecting various amyloid deposits.
In vitro and in vivo assessment of novel derivatives for detecting various amyloid deposits.
复制标题
用于检测各种淀粉样蛋白沉积物的新型衍生物的体外和体内评估。
DOI：
10.1080/13506129.2017.1287070
复制
发表时间：
2017
期刊：
影响因子：
5.5
通讯作者：
Ando Y
中科院分区：
文献类型：
--
作者：
Izaki A;Obayashi K;Suenaga G;Ueda M;Yamashita T;Tasaki M;Yanagisawa Y;Masuda T;Misumi Y;Ando Y
背景合成了多种苯乙烯基苯类化合物，并对其作为Aβ淀粉样蛋白传感器的活性进行了评价。然而，由于这些化合物固有的敏感性，这些化合物不能用于检测外周神经中的淀粉样蛋白沉积。在组织化学研究中，这些化合物通常产生假阳性，尤其是在血管的基底膜中。材料和方法合成了各种对称和不对称的苯乙烯基苯衍生物，然后将这些化合物用于检测来自患有各种全身和局部形式的淀粉样变性如甲状腺素运载蛋白（TTR）相关的家族性淀粉样多发性神经病（FAP），结果1-甲氧基-2，5-二苯乙烯基苯和2-（2-（2-氟乙氧基）乙氧基）乙氧基-2，5-二苯乙烯基苯（EEEFSB）在体外和体内均检测到淀粉样纤维。1-甲氧基-2，5-二苯乙烯基苯也显示了高强度的荧光与周围神经中的FAP患者的淀粉样蛋白沉积。讨论和结论1-甲氧基-2，5-二苯乙烯基苯和EEEFSB可能被证明是一个有用的工具，诊断淀粉样变性，不仅在组织化学研究，而且在全身淀粉样蛋白正电子发射断层扫描（PET）成像。
BackgroundVarious styrylbenzene compounds were synthesized and evaluated as mainly Aβ amyloid sensors. These compounds, however, cannot be used for detecting amyloid deposition in peripheral nerves because of the inherent sensitivity of the compounds. These compounds often generate false positives especially in the basement membrane of blood vessels in histochemical studies. To overcome these problems, we must first synthesize other styryl compounds for detecting amyloid fibrils in tissues.Materials and methodsA wide variety of symmetrical and unsymmetrical styrylbenzene derivatives were synthesized and then these compounds were used to detect amyloid fibrils in autopsy and biopsy samples from patients with various systemic and localized forms of amyloidosis such as transthyretin (TTR)-related familial amyloidotic polyneuropathy (FAP), senile systemic amyloidosis (SSA), amyloid A (AA) amyloidosis, localized AL amyloidosis, and Alzheimer's disease.Results1-Methoxy-2, 5-bis-styrylbenzene and 2-(2-(2-fluoroethoxy) ethoxy) ethoxy)-2, 5-bis-styrylbenzene (EEEFSB) detected amyloid fibrils in both in vitro and in vivo histopathological studies. 1-Methoxy-2, 5-bis-styrylbenzene also showed a high strength of fluorescence with amyloid deposition in peripheral nerves in a patient with FAP.Discussion and conclusions1-Methoxy-2, 5-bis-styrylbenzene and EEEFSB may prove a useful tool for diagnosing amyloidosis, not only in a histochemical study but also in whole body amyloid positron emission tomography (PET) imaging.