DOI: 10.1523/jneurosci.19-24-10627.1999. C Terminus of Presenilin Is Required for Overproduction of Amyloidogenic Aβ42 through Stabilization and Endoproteolysis of Presenilin

C Terminus of Presenilin Is Required for Overproduction of Amyloidogenic Aβ42 through Stabilization and Endoproteolysis of Presenilin

10.1523/jneurosci.19-24-10627.1999

Crossref journal-article

Society for Neuroscience

The Journal of Neuroscience (393)

Abstract

Mutations in presenilin (PS) genes cause early onset familial Alzheimer's disease (FAD) by increasing production of the amyloidogenic form of amyloid β peptides ending at residue 42 (Aβ42). To identify a PS subdomain responsible for overproduction of Aβ42, we analyzed neuro2a cell lines expressing modified forms of PS2 that harbor an N141I FAD mutation. Deletion or addition of amino acids at the C terminus and Ile448 substitution in PS2 with the N141I FAD mutation abrogated the increase in Aβ42 secretion, and Aβ42 overproduction was dependent on the stabilization and endoproteolysis of PS2. The same C-terminal modifications in PS1 produced similar effects. Hence, we suggest that the C terminus of PS plays a crucial role in the overproduction of Aβ42 through stabilization of endoproteolytic PS derivatives and that these derivatives may be the pathologically active species of PS that cause FAD.

Bibliography

Tomita, T., Takikawa, R., Koyama, A., Morohashi, Y., Takasugi, N., Saido, T. C., Maruyama, K., & Iwatsubo, T. (1999). C Terminus of Presenilin Is Required for Overproduction of Amyloidogenic AÎ²42 through Stabilization and Endoproteolysis of Presenilin. The Journal of Neuroscience, 19(24), 10627â10634.

Authors 8

Taisuke Tomita (first)
Rie Takikawa (additional)
Akihiko Koyama (additional)
Yuichi Morohashi (additional)
Nobumasa Takasugi (additional)
Takaomi C. Saido (additional)
Kei Maruyama (additional)
Takeshi Iwatsubo (additional)

References 43 Referenced 89

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Dates

Type	When
Created	7 years, 4 months ago (April 6, 2018, 9:15 p.m.)
Deposited	2 years, 4 months ago (April 13, 2023, 9:09 a.m.)
Indexed	3 months ago (May 20, 2025, 10:32 a.m.)
Issued	25 years, 8 months ago (Dec. 15, 1999)
Published	25 years, 8 months ago (Dec. 15, 1999)
Published Online	25 years, 8 months ago (Dec. 15, 1999)
Published Print	25 years, 8 months ago (Dec. 15, 1999)

Funders 0

None

BibTeX

@article{Tomita_1999, title={C Terminus of Presenilin Is Required for Overproduction of Amyloidogenic Aβ42 through Stabilization and Endoproteolysis of Presenilin}, volume={19}, ISSN={1529-2401}, url={http://dx.doi.org/10.1523/jneurosci.19-24-10627.1999}, DOI={10.1523/jneurosci.19-24-10627.1999}, number={24}, journal={The Journal of Neuroscience}, publisher={Society for Neuroscience}, author={Tomita, Taisuke and Takikawa, Rie and Koyama, Akihiko and Morohashi, Yuichi and Takasugi, Nobumasa and Saido, Takaomi C. and Maruyama, Kei and Iwatsubo, Takeshi}, year={1999}, month=dec, pages={10627–10634} }

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