期刊
JOURNAL OF NEUROSCIENCE
卷 29, 期 5, 页码 1480-1485出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.6202-08.2009
关键词
alpha-synuclein; exocytosis; rab11a; HSP90; Parkinson's disease; synucleinopathy; proteomics
资金
- NIA NIH HHS [R01 AG025327-01, R01 AG033398, R01 AG025327, R01 AG033398-05, AG033398, AG025327] Funding Source: Medline
- NIEHS NIH HHS [R01 ES019277-01A1, R01 ES012703, ES012703, R01 ES019277, R01 ES012703-01A1] Funding Source: Medline
- NINDS NIH HHS [R01 NS057567, NS057567] Funding Source: Medline
Growing evidence suggests that extracellular alpha-synuclein (eSNCA) may play an important role in the pathogenesis of Parkinson's disease (PD) and related synucleinopathies by producing neurotoxicity directly or via activation of glia. However, the mechanisms involved in the trafficking of eSNCA in neurons and/or glia remain unclear. Here, we demonstrated that eSNCA could be resecreted out of neurons via a process modulated by a recycling endosome regulator rab11a in addition to being degraded by an endosome-lysosome system. A quantitative proteomic analysis also revealed numerous proteins through which rab11a might execute its function. One of the candidate proteins, heat shock protein 90 (HSP90), was validated to be interacting with rab11a. Furthermore, geldanamycin, an HSP90 inhibitor, not only prevented resecretion of eSNCA but also attenuated neurotoxicity induced by eSNCA.
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