Department of Neuroscience, Georgetown University Medical Center, Washington, DC 20057, USA.
Int J Mol Sci. 2013 Sep 17;14(9):19109-27. doi: 10.3390/ijms140919109.
Accumulation of misfolded proteins has been implicated in a variety of neurodegenerative diseases including prion diseases, Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). In the past decade, single-chain fragment variable (scFv) -based immunotherapies have been developed to target abnormal proteins or various forms of protein aggregates including Aβ, SNCA, Htt, and PrP proteins. The scFvs are produced by fusing the variable regions of the antibody heavy and light chains, creating a much smaller protein with unaltered specificity. Because of its small size and relative ease of production, scFvs are promising diagnostic and therapeutic reagents for protein misfolded diseases. Studies have demonstrated the efficacy and safety of scFvs in preventing amyloid protein aggregation in preclinical models. Herein, we discuss recent developments of these immunotherapeutics. We review efforts of our group and others using scFv in neurodegenerative disease models. We illustrate the advantages of scFvs, including engineering to enhance misfolded conformer specificity and subcellular targeting to optimize therapeutic action.
错误折叠蛋白的积累与多种神经退行性疾病有关，包括朊病毒病、阿尔茨海默病（AD）、帕金森病（PD）和亨廷顿病（HD）。在过去的十年中，已经开发出基于单链抗体可变区（scFv）的免疫疗法来靶向异常蛋白或各种形式的蛋白聚集体，包括 Aβ、SNCA、Htt 和 PrP 蛋白。scFvs 通过融合抗体重链和轻链的可变区产生，形成一个更小的、特异性不变的蛋白质。由于其体积小且相对易于生产，scFvs 是治疗蛋白错误折叠疾病的有前途的诊断和治疗试剂。研究表明，scFvs 在预防临床前模型中淀粉样蛋白聚集方面具有疗效和安全性。本文讨论了这些免疫疗法的最新进展。我们回顾了我们小组和其他小组在神经退行性疾病模型中使用 scFv 的努力。我们说明了 scFvs 的优势，包括工程设计以增强错误折叠构象特异性和亚细胞靶向以优化治疗作用。
