The prion model for progression and diversity of neurodegenerative diseases
The prion model for progression and diversity of neurodegenerative diseases
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DOI：
10.1016/s1474-4422(17)30037-6
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发表时间：
2017-04-01
期刊：
影响因子：
48
通讯作者：
Diamond, Marc I.
中科院分区：
文献类型：
--
作者：
Stopschinski, Barbara E.;Diamond, Marc I.
不同的神经退行性疾病的神经病理学开始于不同的大脑区域，并涉及不同的大脑网络。有证据表明，蛋白质聚集的跨细胞传播是朊病毒病的基础，可能是神经退行性疾病如阿尔茨海默病、帕金森病和亨廷顿病的病理学进展的基础。朊病毒模型根据病理蛋白的构象预测神经元脆弱性和网络参与的特定模式。事实上，有证据表明，自我传播的聚集体构象异构体，或所谓的菌株，与不同的神经病理综合征。将这一假设扩展到我们对常见神经退行性疾病的理解，可以提出新的治疗方法，如免疫疗法和小分子，以阻止跨细胞传播，以及新的诊断工具来检测疾病的早期证据。
The neuropathology of different neurodegenerative diseases begins in different brain regions, and involves distinct brain networks. Evidence indicates that transcellular propagation of protein aggregation, which is the basis of prion disease, might underlie the progression of pathology in neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, and Huntington's disease. The prion model predicts specific patterns of neuronal vulnerability and network involvement on the basis of the conformation of pathological proteins. Indeed, evidence indicates that self-propagating aggregate conformers, or so-called strains, are associated with distinct neuropathological syndromes. The extension of this hypothesis to our understanding of common neurodegenerative disorders can suggest new therapeutic approaches, such as immunotherapy and small molecules, to block transcellular propagation, and new diagnostic tools to detect early evidence of disease.