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氚标记的(E,E)-2,5-双(4'-羟基-3'-羧基苯乙烯基)苯作为β-淀粉样蛋白原纤维的探针。

Tritium-labeled (E,E)-2,5-bis(4'-hydroxy-3'-carboxystyryl)benzene as a probe for β-amyloid fibrils.

作者信息

Matveev Sergey V, Kwiatkowski Stefan, Sviripa Vitaliy M, Fazio Robert C, Watt David S, LeVine Harry

机构信息

Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536-0509, United States; Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY 40536-0230, United States.

Department of Molecular and Cellular Biochemistry, College of Medicine, University of Kentucky, Lexington, KY 40536-0509, United States; Center for Pharmaceutical Research and Innovation, College of Pharmacy, University of Kentucky, Lexington, KY 40536-0596, United States.

出版信息

Bioorg Med Chem Lett. 2014 Dec 1;24(23):5534-6. doi: 10.1016/j.bmcl.2014.09.075. Epub 2014 Oct 6.

Abstract

Accumulation of Aβ in the brains of Alzheimer disease (AD) patients reflects an imbalance between Aβ production and clearance from their brains. Alternative cleavage of amyloid precursor protein (APP) by processing proteases generates soluble APP fragments including the neurotoxic amyloid Aβ40 and Aβ42 peptides that assemble into fibrils and form plaques. Plaque-buildup occurs over an extended time-frame, and the early detection and modulation of plaque formation are areas of active research. Radiolabeled probes for the detection of amyloid plaques and fibrils in living subjects are important for noninvasive evaluation of AD diagnosis, progression, and differentiation of AD from other neurodegenerative diseases and age-related cognitive decline. Tritium-labeled (E,E)-1-[(3)H]-2,5-bis(4'-hydroxy-3'-carbomethoxystyryl)benzene possesses an improved level of chemical stability relative to a previously reported radioiodinated analog for radiometric quantification of Aβ plaque and tau pathology in brain tissue and in vitro studies with synthetic Aβ and tau fibrils.

摘要

阿尔茨海默病(AD)患者大脑中β淀粉样蛋白(Aβ)的积累反映了Aβ生成与从大脑清除之间的失衡。淀粉样前体蛋白(APP)通过加工蛋白酶进行的选择性切割产生可溶性APP片段,包括神经毒性淀粉样Aβ40和Aβ42肽,它们组装成纤维并形成斑块。斑块的形成是一个长期的过程,早期检测和调节斑块形成是当前积极研究的领域。用于检测活体受试者中淀粉样斑块和纤维的放射性标记探针对于AD诊断、病情进展以及AD与其他神经退行性疾病和年龄相关认知衰退的鉴别诊断的无创评估具有重要意义。相对于先前报道的用于脑组织中Aβ斑块和tau病理学放射性定量以及与合成Aβ和tau纤维进行体外研究的放射性碘化类似物,氚标记的(E,E)-1-[(3)H]-2,5-双(4'-羟基-3'-甲氧羰基苯乙烯基)苯具有更高的化学稳定性。

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