Antagonizing Neuronal Toll-like Receptor 2 Prevents Synucleinopathy by Activating Autophagy.
Antagonizing Neuronal Toll-like Receptor 2 Prevents Synucleinopathy by Activating Autophagy.
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DOI：
10.1016/j.celrep.2015.09.044
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发表时间：
2015-10-27
期刊：
影响因子：
8.8
通讯作者：
Masliah E
中科院分区：
文献类型：
--
作者：
Kim C;Rockenstein E;Spencer B;Kim HK;Adame A;Trejo M;Stafa K;Lee HJ;Lee SJ;Masliah E
Impaired autophagy has been implicated in many neurodegenerative diseases, such as Parkinson's disease (PD), and might be responsible for deposition of aggregated proteins in neurons. However, little is known how neuronal autophagy and clearance of aggregated proteins are regulated. Here, we show a role for Toll-like receptor 2 (TLR2), a pathogen-recognizing receptor in innate immunity, in regulation of neuronal autophagy and clearance of α-synuclein, a protein aggregated in synucleinopathies, including PD. Activation of TLR2 resulted in accumulation of α-synuclein aggregates in neurons as a result of inhibition of autophagic activity through regulation of the AKT/mTOR pathway. In contrast, inactivation of TLR2 resulted in autophagy activation and increased clearance of neuronal α-synuclein, hence reduced neurodegeneration, in transgenic mice and in in vitro models. These results uncover novel roles of TLR2 in regulating neuronal autophagy, and the TLR2 pathway may be targeted for the autophagy activation strategies in treating neurodegenerative disorders.
