Intercellular Spread of Protein Aggregates in Neurodegenerative Disease.
Intercellular Spread of Protein Aggregates in Neurodegenerative Disease.
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DOI：
10.1146/annurev-cellbio-100617-062636
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发表时间：
2018-10-06
影响因子：
11.3
通讯作者：
Holtzman DM
中科院分区：
文献类型：
--
作者：
Davis AA;Leyns CEG;Holtzman DM
大多数神经退行性疾病的特征是蛋白质聚集体的积累，其中一些对细胞有毒性。越来越多的证据表明，在几种疾病中，蛋白质聚集体可以沿着连接的网络从一个神经元传递到另一个神经元，尽管这种传播现象在疾病发病机制中的作用尚未完全了解。在此，我们简要回顾神经退行性疾病中蛋白质聚集的分子和组织病理学特征，总结蛋白质从供体细胞释放到细胞外空间的证据，并强调蛋白质聚集体可能传递到受体细胞的一些其他机制。我们还讨论了支持蛋白质聚集体传播在神经退行性疾病发病机制中起作用的证据以及该模型的一些局限性。最后，我们考虑在神经退行性疾病治疗中针对蛋白质聚集体传播的潜在治疗策略。
Most neurodegenerative diseases are characterized by the accumulation of protein aggregates, some of which are toxic to cells. Mounting evidence demonstrates that in several diseases, protein aggregates can pass from neuron to neuron along connected networks, although the role of this spreading phenomenon in disease pathogenesis is not completely understood. Here we briefly review the molecular and histopathological features of protein aggregation in neurodegenerative disease, we summarize the evidence for release of proteins from donor cells into the extracellular space, and we highlight some other mechanisms by which protein aggregates might be transmitted to recipient cells. We also discuss the evidence that supports a role for spreading of protein aggregates in neurodegenerative disease pathogenesis and some limitations of this model. Finally, we consider potential therapeutic strategies to target spreading of protein aggregates in the treatment of neurodegenerative diseases.
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