Self-propagation of pathogenic protein aggregates in neurodegenerative diseases.
Self-propagation of pathogenic protein aggregates in neurodegenerative diseases.
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作者：
几十年来，科学家们一直推测，理解与年龄相关的神经退行性疾病的关键可能在于朊病毒疾病的不寻常生物学。最近，主要是由于新的疾病模型的出现，这一假设已获得实验动力。在各种各样的疾病中，已经发现特定的蛋白质错误折叠并聚集成种子，这些种子在结构上破坏了类似的蛋白质，导致它们聚集并形成从小的寡聚体到大质量的淀粉样蛋白的致病性组装体。因此，蛋白质种子可以作为疾病的煽动和进展的自繁殖剂。阿尔茨海默氏病和其他脑蛋白质病似乎是由内源性蛋白质的重新错误折叠和持续腐败引起的，而朊病毒疾病也可能是传染性的。然而，在所有情况下的结果是神经系统的功能损害，因为聚集的蛋白质获得毒性功能和/或失去其正常功能。作为一种统一的致病原理，朊病毒范式为目前一大类难治性疾病提出了广泛相关的治疗方向。
For several decades scientists have speculated that the key to understanding age-related neurodegenerative disorders may be found in the unusual biology of the prion diseases. Recently, owing largely to the advent of new disease models, this hypothesis has gained experimental momentum. In a remarkable variety of diseases, specific proteins have been found to misfold and aggregate into seeds that structurally corrupt like proteins, causing them to aggregate and form pathogenic assemblies ranging from small oligomers to large masses of amyloid. Proteinaceous seeds can therefore serve as self-propagating agents for the instigation and progression of disease. Alzheimer’s disease and other cerebral proteopathies seem to arise from the de novo misfolding and sustained corruption of endogenous proteins, whereas prion diseases can also be infectious in origin. However, the outcome in all cases is the functional compromise of the nervous system, because the aggregated proteins gain a toxic function and/or lose their normal function. As a unifying pathogenic principle, the prion paradigm suggests broadly relevant therapeutic directions for a large class of currently intractable diseases.
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影响因子：
13.8
作者：
Dobson, CM
通讯作者：
Dobson, CM
影响因子：
11.8
作者：
Brown P;Brandel JP;Sato T;Nakamura Y;MacKenzie J;Will RG;Ladogana A;Pocchiari M;Leschek EW;Schonberger LB
通讯作者：
Schonberger LB
影响因子：
16.6
作者：
Caughey B;Baron GS;Chesebro B;Jeffrey M
通讯作者：
Jeffrey M
DOI：
10.1074/jbc.m112.340638
发表时间：
2012-08-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Ano Bom AP;Rangel LP;Costa DC;de Oliveira GA;Sanches D;Braga CA;Gava LM;Ramos CH;Cepeda AO;Stumbo AC;De Moura Gallo CV;Cordeiro Y;Silva JL
通讯作者：
Silva JL
影响因子：
25
作者：
Bero AW;Yan P;Roh JH;Cirrito JR;Stewart FR;Raichle ME;Lee JM;Holtzman DM
通讯作者：
Holtzman DM