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An alternative spliced mouse presenilin-2 mRNA encodes a novel γ-secretase inhibitor
The γ-secretase, composed of presenilin-1 (PS1) or presenilin-2 (PS2), nicastrin (NCT), anterior pharynx-defective phenotype 1 (APH-1), and PEN-2, is critical for the development of Alzheimer’s disease (AD). PSs are autoproteolytically cleaved, producing an N-terminal fragment (NTF) and a hydrophili...
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Published in: | FEBS letters 2009-05, Vol.583 (9), p.1403-1408 |
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Main Authors: | , , , , , , , , , , , |
Format: | Article |
Language: | English |
Subjects: | |
Citations: | Items that this one cites Items that cite this one |
Online Access: | Get full text |
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Summary: | The γ-secretase, composed of presenilin-1 (PS1) or presenilin-2 (PS2), nicastrin (NCT), anterior pharynx-defective phenotype 1 (APH-1), and PEN-2, is critical for the development of Alzheimer’s disease (AD). PSs are autoproteolytically cleaved, producing an N-terminal fragment (NTF) and a hydrophilic loop domain-containing C-terminal fragment. However, the role of the loop domain in the γ-secretase complex assembly remains unknown. Here, we report a novel PS2 isoform generated by alternative splicing, named PS2β, which is composed of an NTF with a hydrophilic loop domain. PS2β disturbed the interaction between NCT and APH-1, resulting in the inhibition of amyloid-β production. We concluded that PS2β may inhibit γ-secretase activity by affecting the γ-secretase complex assembly.
MINT-
7025654:
APH1 (uniprotkb:
Q96BI3)
physically interacts (MI:
0218) with
PEN2 (uniprotkb:
Q9NZ42),
PS2 beta (uniprotkb:
Q61144-2) and
PS1 (uniprotkb:
P49769) by
anti tag coimmunoprecipitation (MI:
0007)
MINT-
7025631:
APH1 (uniprotkb:
Q96BI3)
physically interacts (MI:
0218) with
NCT (uniprotkb:
Q92542),
PEN2 (uniprotkb:
Q9NZ42) and
PS1 (uniprotkb:
P49769) by
anti tag coimmunoprecipitation (MI:
0007) |
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ISSN: | 0014-5793 1873-3468 |
DOI: | 10.1016/j.febslet.2009.04.014 |