Department of Neuroscience, College of Medicine, McKnight Brain Institute, University of Florida, Gainesville, FL, USA.
Autophagy. 2011 Feb;7(2):238-9. doi: 10.4161/auto.7.2.14278. Epub 2011 Feb 1.
Demyelinating peripheral neuropathies associated with abnormal expression of peripheral myelin protein 22 (PMP22) involve the formation of cytosolic protein aggregates within Schwann cells. Towards developing a therapy for these progressive neurodegenerative diseases, we assessed whether pharmacological activation of autophagy by rapamycin (RM) could prevent protein aggregation and enhance Schwann cell myelination. Indeed, we found that glial cells from neuropathic mice activate autophagy in response to RM and produce abundant myelin internodes. Lentivirus-mediated shRNA shutdown of Atg12 abrogates the improvements in myelin production, demonstrating that autophagy is critical for the observed benefits.
与外周髓鞘蛋白 22（PMP22）异常表达相关的脱髓鞘周围神经病涉及施万细胞内细胞溶质蛋白聚集体的形成。为了开发针对这些进行性神经退行性疾病的治疗方法，我们评估了雷帕霉素（RM）通过激活自噬是否可以防止蛋白聚集并增强施万细胞髓鞘形成。事实上，我们发现神经病变小鼠的神经胶质细胞在 RM 作用下激活自噬并产生大量髓鞘节段。慢病毒介导的 Atg12 shRNA 敲低会破坏髓鞘产生的改善，表明自噬对观察到的益处至关重要。
