Ginkgolide K promotes the clearance of A53T mutation alpha-synuclein in SH-SY5Y cells.
Wenbo YuSheng ChenLiang CaoJie TangWei XiaoBao-Guo XiaoPublished in: Cell biology and toxicology (2017)
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.
Keyphrases
- cell death
- cell cycle arrest
- signaling pathway
- induced apoptosis
- pi k akt
- endoplasmic reticulum stress
- cell proliferation
- oxidative stress
- high glucose
- diabetic rats
- drug induced
- combination therapy
- immune response
- epithelial mesenchymal transition
- cell cycle
- climate change
- replacement therapy
- inflammatory response
- stress induced
- toll like receptor