Abstract
Alpha-synuclein (α-syn) is associated to Parkinson’s disease (PD). The aggregated form of α-syn has potential neurotoxicity. Thus, the clearance of α-syn aggregation is a plausible strategy to delay disease progression of PD. In our study, we found that the treatment of Ginkgolide B (GB) and Ginkgolide K (GK) reduced cell death, and enhanced cell proliferation in SH-SY5Y cells, which overexpressed A53T mutant α-syn. Surprisingly, GK, but not GB, promoted the clearance of A53T α-syn, which can be abolished by autophagy inhibitor 3-methyladenine, indicating that GK-induced autophagy intervened in the clearance of A53T α-syn. However, GK did not affect the NEDD4 that belongs to the ubiquitin ligase in the endosomal–lysosomal pathway. Furthermore, GK treatment inhibited the p-NF-kB/p65 and induced the PI3K, BDNF, and PSD-95. Taken together, GK increased the clearance of α-syn, reduced cell death, and triggered complex crosstalk between different signaling pathways. Although our results show a potentially new therapeutic candidate for PD, the details of this mechanism need to be further identified.
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This work was supported by grants from the National Natural Science Foundation of China (No. 81371414) and National Major Scientific and Technological Special Project for significant new drug development (2013ZX09402203).
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Yu, W., Chen, S., Cao, L. et al. Ginkgolide K promotes the clearance of A53T mutation alpha-synuclein in SH-SY5Y cells. Cell Biol Toxicol 34, 291–303 (2018). https://doi.org/10.1007/s10565-017-9419-4
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DOI: https://doi.org/10.1007/s10565-017-9419-4