Abstract
PEN-2 is a component of the γ-secretase complex, which is involved in the cleavage of the β-amyloid precursor protein. The aim of this study was to determine the mechanism by which PEN-2 overexpression regulates γ-secretase expression and the production of Aβ-42. In order to determine this, a hybrid gene harboring human PEN-2 was constructed, and used in the transfection of SK-N-MC human neuroepitheliomal cells. This cell line was also co-transfected with a combination of human mutant presenilin 2 (hPS2m) and APPsw. Our results indicated that (i) human PEN-2 overexpression induced an increase in γ-secretase activity and its proteins, including PS1-CTF, APH-1, and nicastrin, thus production of Aβ-42, (ii) co-transfection of human PEN-2 with both hPS2m and APPsw exerted no more profound effects on the induction of γ-secretase proteins and its activity than did transfection with hPEN-2 alone. Thus, PEN-2 overexpression may facilitate assembly into the more active γ-secretase complex, and may also induce an increase in activity, thus affecting Aβ-42 production.
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Acknowledgments
This research was supported by grants to Dr. Yong K. Kim from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (A040042) and the Korea FDA.
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Seo, S.J., Hwang, D.Y., Cho, J.S. et al. PEN-2 Overexpression Induces γ-Secretase Protein and its Activity with Amyloid β-42 Production. Neurochem Res 32, 1016–1023 (2007). https://doi.org/10.1007/s11064-006-9262-0
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DOI: https://doi.org/10.1007/s11064-006-9262-0