Sumoylation이 beta-secretase 활성에 미치는 영향

초록

Purpose : A key neuropathological event in Alzheimer's disease(AD) is the cerebral accumulation of an ~4kDa peptide termed Abeta, the principle component of senile plaques. The Abeta peptide is derived by serial proteolysis of APP through BACE and gamma-secretase. It has also shown that the BACE protein levels are accumulated in AD brain and APP transgenic mice brains. In the current study, we investigated the mechanism to induce accumulation of BACE in brain. Methods : H4 human neuroglioma cells were maintained in DMEM with 10% FBS and antibiotics. Various plasmid DNAs were transfected in subconflunet cells using superfect, lipofectamin. Cell extracts were prepared in modified RIPA buffer. The expression pattern analysis of SUMO and BACE were performed by immunocytochemistry or western blot. Results : Sumoylation of BACE could be detected in H4 cells transfected BACE and SUMO using in vitro assay. Although SUMO did not affect APP full length, SUMO increased BACE level and Abeta production. Furthermore, SUMO induced the alteration of BACE subcellular localization. The levels of secreted soluble APP were also affected by transfection of SUMO. Conclusions : These result implicate that SUMO may regulates amyloid beta peptides production through indirect regulation of BACE or APP processing.

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