Development of Vaccination Approaches for the Treatment of Neurological Diseases
Development of Vaccination Approaches for the Treatment of Neurological Diseases
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DOI：
10.1002/cne.22034
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发表时间：
2009-07-01
影响因子：
2.5
通讯作者：
Federoff，Howard J.
中科院分区：
文献类型：
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作者：
Federoff，Howard J.
几种进行性神经退行性疾病都有一个共同的病理：错误折叠的蛋白质在脑细胞或神经束内堆积。这些错误折叠的蛋白质形成了具有淀粉样蛋白光学和生化特性的有组织的β片状组合体。因此，脑淀粉样变性、阿尔茨海默病(AD)、帕金森氏病(Parkinson‘s)和普里诺病(Prionoses)或可传播海绵状脑病(TSE)都表现出可能致病的错误折叠蛋白，这表明这些蛋白或其前体可能是治疗开发努力的靶点。这本专著讨论了两种不同的生物学方法，都是基于疫苗接种，作为治疗AD和TSE的临床前方法。在这里，我首先描述了一种积极的疫苗接种方法，它利用免疫成形在AD小鼠模型中产生预防性的TH2对Aβ的反应。其次，我描述了一种被动免疫策略，在小鼠TSE模型中，通过重组腺相关病毒载体递送抗Prion单链片段可变抗体来减缓疾病进展并促进寿命延长。J.Comp.神经。515：4-14,2009。©2009威利-利斯，Inc.
Several progressive neurodegenerative diseases share a common pathology: the accumulation of misfolded proteins within cells or neuropil of the brain. Characteristically, these misfolded proteins form organized β‐sheet‐containing assemblies that have optical and biochemical properties of amyloid. Thus, the brain amyloidoses, Alzheimer's disease (AD), Parkinson's disease, and the prionoses or transmissible spongioform encelphalopathies (TSEs) all manifest putatively pathogenic misfolded proteins, suggesting that these proteins or their precursors may be targets for therapeutics development efforts. Two different biological approaches, both predicated on vaccination, are discussed in this monograph as preclinical approaches for the treatment of AD and a TSE. Herein, I first describe an active vaccination approach that exploits immune shaping to engender a prophylactic TH2 response to Aβ in AD mouse models. Second, I describe a passive vaccination strategy whereby recombinant adeno‐associated virus vectored delivery of anti‐prion single‐chain fragment variable antibodies attenuates disease progression and promotes life extension in a mouse TSE model. J. Comp. Neurol. 515:4–14, 2009. © 2009 Wiley‐Liss, Inc.