Format

Send to

Choose Destination
Neurochem Res. 2007 Jun;32(6):1016-23. Epub 2007 Mar 31.

PEN-2 overexpression induces gamma-secretase protein and its activity with amyloid beta-42 production.

Author information

1
Division of Laboratory Animal Resources, National Institute of Toxicological Research, Korea FDA, 5 Nokbun-dong Eunpyng-ku, Seoul, Korea.

Abstract

PEN-2 is a component of the gamma-secretase complex, which is involved in the cleavage of the beta-amyloid precursor protein. The aim of this study was to determine the mechanism by which PEN-2 overexpression regulates gamma-secretase expression and the production of Abeta-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 gamma-secretase activity and its proteins, including PS1-CTF, APH-1, and nicastrin, thus production of Abeta-42, (ii) co-transfection of human PEN-2 with both hPS2m and APPsw exerted no more profound effects on the induction of gamma-secretase proteins and its activity than did transfection with hPEN-2 alone. Thus, PEN-2 overexpression may facilitate assembly into the more active gamma-secretase complex, and may also induce an increase in activity, thus affecting Abeta-42 production.

PMID:
17401676
DOI:
10.1007/s11064-006-9262-0
[Indexed for MEDLINE]

Supplemental Content

Full text links

Icon for Springer
Loading ...
Support Center