细胞间蛋白聚集物在神经退行性疾病中的传播。
Intercellular Spread of Protein Aggregates in Neurodegenerative Disease.
机构信息
Department of Neurology, Washington University School of Medicine, St. Louis, Missouri 63110, USA; email:
Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, Missouri 63110, USA.
出版信息
Annu Rev Cell Dev Biol. 2018 Oct 6;34:545-568. doi: 10.1146/annurev-cellbio-100617-062636. Epub 2018 Jul 25.
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.
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。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神经元传递到神经元，尽管这种传播现象在疾病发病机制中的作用尚不完全清楚。在这里，我们简要回顾了神经退行性疾病中蛋白质聚集的分子和组织病理学特征，总结了蛋白质从供体细胞释放到细胞外空间的证据，并强调了蛋白质聚集体可能传递给受体细胞的其他一些机制。我们还讨论了支持蛋白质聚集体在神经退行性疾病发病机制中传播作用的证据，以及该模型的一些局限性。最后，我们考虑了针对神经退行性疾病中蛋白质聚集体传播的潜在治疗策略。
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