Evidence map›Paper›PMID 35764706›Full record

ArticleMolecular psychiatry2022

Hypoxia Inducible Factor-1α binds and activates γ-secretase for Aβ production under hypoxia and cerebral hypoperfusion.

Courtney Alexander, Thomas Li, Yorito Hattori, Danica Chiu, Georgia R Frost, Lauren Jonas, Chenge Liu, Corey J Anderson, Eitan Wong, Laibaik Park and 2 more

Open access · greenAbstract read
In one paragraph

Article in Molecular psychiatry, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed, 1 pooled it
4.8field-weighted citation impact, top 4% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

29 citing papers in PubMed, 1 synthesis or guideline pooled it, 45 citations in OpenAlex.

  1. The Role of c-Abl in Alzheimer's Disease: Guilty or not Guilty?Cellular and molecular neurobiology · 2025
    Pooled it
  2. Review
  3. Review
  4. Review
  5. The bidirectional mechanistic links between Alzheimer's disease and cardiovascular disease.Neurological sciences : official journal of the Italian Neurological Society and of the Italian Society of Clinical Neurophysiology · 2026
    Review
  6. Review
  7. Review
  8. Review
  9. Article
  10. Article
  11. Review
  12. From defense to disease: IFITM3 in immunity and Alzheimer's disease.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2025
    Review
  13. Article
  14. Article
  15. Review
  16. Total flavonoids ofFrontiers in pharmacology · 2025
    Article
  17. Article
  18. Review
  19. Article
  20. The Azalea Hypothesis of Alzheimer Disease: A Functional Iron Deficiency Promotes Neurodegeneration.The Neuroscientist : a review journal bringing neurobiology, neurology and psychiatry · 2024
    Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 2 institutions in 1 country.

Courtney Alexander *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0003-3718-5769
Thomas Li *Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.ORCID http://orcid.org/0000-0002-4207-4652
Yorito HattoriFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Danica ChiuChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Georgia R FrostChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Lauren JonasChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Chenge LiuChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Corey J AndersonPrograms of Neurosciences and Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.
Eitan WongChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA.
Laibaik ParkFeil Family Brain and Mind Research Institute, Weill Cornell Medicine, New York, NY, USA.
Costantino IadecolaPrograms of Neurosciences and Weill Graduate School of Medical Sciences of Cornell University, New York, NY, USA.ORCID http://orcid.org/0000-0001-9797-073X
Yue-Ming LiChemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY, USA. liy2@mskcc.org.ORCID http://orcid.org/0000-0002-2633-3730
Memorial Sloan Kettering Cancer Center · USCornell University · US

Funding

X-RAY CRYSTALLOGRAPHYP30CA008748 · NCI · SLOAN-KETTERING INSTITUTE FOR CANCER RES · PI SELWYN M VICKERS · 1985 to 2026
$347.4M
CANCER PHARMACOLOGYT32CA062948 · NCI · WEILL MEDICAL COLL OF CORNELL UNIV · PI LORRAINE J GUDAS · 1994 to 2026
$12.1M
Overexpression of the amyloid precursor protein and cerebrovascular regulationR01NS037853 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Costantino Iadecola · 1998 to 2026
$10.6M
NO SYNTHASE GENE EXPRESSION AND CEREBRAL ISCHEMIC DAMAGER01NS034179 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI IADECOLA, COSTANTINO · 1995 to 2021
$5.5M
Regulation of y-secretase activity by modulatory proteinsR01AG061350 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI LI, YUEMING · 2019 to 2023
$4.3M
ApoE4, Neurovascular Injury and Cognitive ImpairmentR01NS126467 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI Costantino Iadecola · 2022 to 2026
$4.1M
ApoE4 and mechanisms of diffuse white matter injuryR01NS100447 · NINDS · WEILL MEDICAL COLL OF CORNELL UNIV · PI IADECOLA, COSTANTINO · 2016 to 2020
$3.5M
Molecular mechanisms of gamma-secretase modulation central to Alzheimer’s diseaseR01AG080684 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI Liang Feng, YUEMING LI · 2023 to 2026
$3.2M
Substrate Feedback Mechanism of gamma-SecretaseRF1AG057593 · NIA · SLOAN-KETTERING INST CAN RESEARCH · PI LI, YUEMING · 2018 to 2018
$2.1M
Mechanism and Synergy of gamma-Secretase ModulatorsR01NS096275 · NINDS · SLOAN-KETTERING INST CAN RESEARCH · PI LI, YUEMING · 2016 to 2020
$2.1M
NCI NIH HHS P30 CA008748NCI NIH HHS T32 CA062948NIA NIH HHS R01 AG061350NIA NIH HHS R01 AG080684NIA NIH HHS RF1 AG057593NINDS NIH HHS R01 NS034179NINDS NIH HHS R01 NS037853NINDS NIH HHS R01 NS096275NINDS NIH HHS R01 NS100447NINDS NIH HHS R01 NS126467
6 · The paper itself

Abstract

Hypoxic-ischemic injury has been linked with increased risk for developing Alzheimer's disease (AD). The underlying mechanism of this association is poorly understood. Here, we report distinct roles for hypoxia-inducible factor-1α (Hif-1α) in the regulation of BACE1 and γ-secretase activity, two proteases involved in the production of amyloid-beta (Aβ). We have demonstrated that Hif-1α upregulates both BACE1 and γ-secretase activity for Aβ production in brain hypoxia-induced either by cerebral hypoperfusion or breathing 10% O

Indexed as

Alzheimer DiseaseAmyloid Precursor Protein SecretasesHypoxia-Inducible Factor 1, alpha SubunitAmyloid beta-PeptidesAnimalsAspartic Acid EndopeptidasesHypoxiaMiceAmyloid beta-PeptidesAmyloid Precursor Protein SecretasesAspartic Acid EndopeptidasesHif1a protein, mouseHypoxia-Inducible Factor 1, alpha Subunit

Identifiers

PMID35764706
PMCPMC9722522
OpenAlexW4283640437

What Socratic holds

Textmetadata
LicenceTDM
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.