Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 421

The DOI matches its Crossref record; 19 of the 19 references it cites were found in a registry or an index.

Phosphorylation of the Translation Initiation Factor eIF2α Increases BACE1 Levels and Promotes Amyloidogenesis

Open access
O'Connor, Tracy, Sadleir, Katherine R., Maus, Erika, Velliquette, Rodney A., Zhao, Jie, Cole, Sarah L., Eimer, William A., Hitt, Brian, Bembinster, Leslie A., Lammich, Sven, Lichtenthaler, Stefan F., Hébert, Sébastien S., De Strooper, Bart, Haass, Christian, Bennett, David A., Vassar, Robert·2008·Neuron
DOI 10.1016/j.neuron.2008.10.047
Open this paper in CoChat — free account

Abstract

Summary Beta-site APP cleaving enzyme-1 (BACE1), the rate-limiting enzyme for β-amyloid (Aβ) production, is elevated in Alzheimer’s disease (AD). Here, we show that energy deprivation induces phosphorylation of the translation initiation factor eIF2α eIF2α-P), which increases the translation of BACE1. Salubrinal, an inhibitor of eIF2α-P phosphatase PP1c, directly increases BACE1 and elevates Aβ production in primary neurons. Preventing eIF2α phosphorylation by transfection with constitutively active PP1c regulatory subunit, dominant negative eIF2α kinase PERK, or PERK inhibitor P58IPK blocks the energy deprivation-induced BACE1 increase. Furthermore, chronic treatment of aged Tg2576 mice with energy inhibitors increases levels of eIF2α-P, BACE1, Aβ, and amyloid plaques. Importantly, eIF2α-P and BACE1 are elevated in aggressive plaque-forming 5XFAD transgenic mice, and BACE1, eIF2α-P, and amyloid load are all correlated in humans with AD. These results strongly suggest that eIF2α phosphorylation increases BACE1 levels and causes Aβ overproduction, which could be an early, initiating molecular mechanism in sporadic AD.

Overview

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.1016/j.neuron.2008.10.047

Cites

19 of 19 references verified0 citation errors · 0 not checkable

Statistics

Verification

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Citations

Cites

Show all 19 references

Cited by

Metadata

Authors
O'Connor, T., Sadleir, K. R., Maus, E., Velliquette, R. A., Zhao, J., Cole, S. L., Eimer, W. A., Hitt, B., Bembinster, L. A., Lammich, S., Lichtenthaler, S. F., Hébert, S. S., De Strooper, B., Haass, C., Bennett, D. A., & Vassar, R.
Venue
Neuron
Publisher
Elsevier BV
Published
2008-12
Volume
60
Issue
6
Pages
988-1009
ISSN
0896-6273 (ISSN-L)
DOI
10.1016/j.neuron.2008.10.047
OpenAlex
W2088835723
Cited by
421
References
19
FWCI
11.86
Type
journal article
Language
en
Open access
bronze

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.