文章基本信息

标题：Polo-like kinase 2 regulates selective autophagic α-synuclein clearance and suppresses its toxicity in vivo
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作者：Abid Oueslati ; Bernard L. Schneider ; Patrick Aebischer 等
期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2013
卷号：110
期号：41
页码：E3945-E3954
DOI：10.1073/pnas.1309991110
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：An increase in -synuclein levels due to gene duplications/triplications or impaired degradation is sufficient to trigger its aggregation and cause familial Parkinson disease (PD). Therefore, lowering -synuclein levels represents a viable therapeutic strategy for the treatment of PD and related synucleinopathies. Here, we report that Polo-like kinase 2 (PLK2), an enzyme up-regulated in synucleinopathy-diseased brains, interacts with, phosphorylates and enhances -synuclein autophagic degradation in a kinase activity-dependent manner. PLK2-mediated degradation of -synuclein requires both phosphorylation at S129 and PLK2/-synuclein complex formation. In a rat genetic model of PD, PLK2 overexpression reduces intraneuronal human -synuclein accumulation, suppresses dopaminergic neurodegeneration, and reverses hemiparkinsonian motor impairments induced by -synuclein overexpression. This PLK2-mediated neuroprotective effect is also dependent on PLK2 activity and -synuclein phosphorylation. Collectively, our findings demonstrate that PLK2 is a previously undescribed regulator of -synuclein turnover and that modulating its kinase activity could be a viable target for the treatment of synucleinopathies.
关键词：adeno-associated virus ; animal model ; serum inducible kinase