Protein aggregate spreading in neurodegenerative diseases: problems and perspectives.
Protein aggregate spreading in neurodegenerative diseases: problems and perspectives.
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DOI：
10.1016/j.neures.2011.05.008
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发表时间：
2011-08
影响因子：
2.9
通讯作者：
Lee HJ
中科院分区：
文献类型：
--
作者：
Lee SJ;Lim HS;Masliah E;Lee HJ
特异性蛋白质聚集体的进行性积累是许多主要神经退行性疾病的定义特征，包括阿尔茨海默病、帕金森病、额颞叶痴呆、亨廷顿病和克雅氏病（CJD）。最近几项研究的结果表明，易于聚集的蛋白质，如tau蛋白、α-突触核蛋白、含聚谷氨酰胺的蛋白质和淀粉样蛋白-β，可以扩散到其他细胞和大脑区域，这是朊病毒疾病所特有的现象，如CJD和牛海绵状脑病。蛋白质聚集体的细胞间增殖可能是神经退行性疾病进行性恶化的一般基本原理。这也可能在细胞替代疗法中具有重要意义，正如帕金森病患者长期移植中α-突触核蛋白聚集体从宿主向移植细胞的传播所证明的那样。在这里，我们回顾了蛋白质聚集体的实验模型系统中的传播的最新进展，并讨论了突出的问题和未来的前景。了解这种病理性传播的机制可能会为蛋白质错误折叠相关神经退行性疾病的诊断技术和新疗法的发展提供独特的机会。
Progressive accumulation of specific protein aggregates is a defining feature of many major neurodegenerative diseases, including Alzheimer’s disease, Parkinson’s disease, fronto-temporal dementia, Huntington’s disease, and Creutzfeldt–Jakob disease (CJD). Findings from several recent studies have suggested that aggregation-prone proteins, such as tau, α-synuclein, polyglutamine-containing proteins, and amyloid-β, can spread to other cells and brain regions, a phenomenon considered unique to prion disorders, such as CJD and bovine spongiform encephalopathy. Cell-to-cell propagation of protein aggregates may be the general underlying principle for progressive deterioration of neurodegenerative diseases. This may also have significant implications in cell replacement therapies, as evidenced by the propagation of α-synuclein aggregates from host to grafted cells in long-term transplants in Parkinson’s patients. Here, we review recent progress in protein aggregate propagation in experimental model systems and discuss outstanding questions and future perspectives. Understanding the mechanisms of this pathological spreading may open the way to unique opportunities for development of diagnostic techniques and novel therapies for protein misfolding-associated neurodegenerative diseases.
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影响因子：
4.8
作者：
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通讯作者：
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DOI：
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