Evidence map›Paper›PMID 25903103›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2015

γ-Secretase modulators reduce endogenous amyloid β42 levels in human neural progenitor cells without altering neuronal differentiation.

Carla D'Avanzo, Christopher Sliwinski, Steven L Wagner, Rudolph E Tanzi, Doo Yeon Kim, Dora M Kovacs

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.

0numbers the graph read from it
0cells of the map it votes in
8citing papers in PubMed
–field-weighted citation impact
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

8 citing papers in PubMed.

  1. Neural Stem/Progenitor Cell (NSPC) Extraction and Culture.Methods in molecular biology (Clifton, N.J.) · 2024
    Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Review
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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

6 authors.

Carla D'Avanzo*Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA; and Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Christopher Sliwinski*Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA; and Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Steven L Wagner*Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA; and Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Rudolph E Tanzi*Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA; and Department of Neurosciences, University of California, San Diego, La Jolla, California, USA.
Doo Yeon Kim*Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA; and Department of Neurosciences, University of California, San Diego, La Jolla, California, USA dkim@helix.mgh.harvard.edu dora_kovacs@hms.harvard.edu.
Dora M Kovacs*Genetics and Aging Research Unit, MassGeneral Institute for Neurodegenerative Disease, Massachusetts General Hospital, Harvard Medical School, Charlestown, Massachusetts, USA; and Department of Neurosciences, University of California, San Diego, La Jolla, California, USA dkim@helix.mgh.harvard.edu dora_kovacs@hms.harvard.edu.

Funding

TRANSGENICS AND PRESENILIN FUNCTIONP01AG015379 · NIA · BRIGHAM AND WOMEN'S HOSPITAL · PI BEREZOVSKA, OKSANA, SELKOE, DENNIS J · 1998 to 2023
$51.3M
THE ROLE OF ADVANCED CAA IN ALZHEIMER'S DEMENTIAP50AG005134 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI HYMAN, BRADLEY T. · 1985 to 2018
$42.1M
Research Education ComponentP30AG062421 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI Christine S Ritchie · 2019 to 2026
$36.5M
Role of the g-secretase/PS1 complex in APP processingR01AG014713 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI KIM, DOO YEON · 1997 to 2018
$5.9M
A novel human 3D neural cell culture system for the characterization of AD genesRF1AG048080 · NIA · MASSACHUSETTS GENERAL HOSPITAL · PI KIM, DOO YEON, TANZI, RUDOLPH EMILE · 2014 to 2014
$2.1M
NIA NIH HHS 1RF1AG048080-01NIA NIH HHS 2R01AG014713NIA NIH HHS 5P01AG015379NIA NIH HHS P01 AG015379NIA NIH HHS P30 AG062421NIA NIH HHS P50 AG005134NIA NIH HHS R01 AG014713NIA NIH HHS RF1 AG048080
6 · The paper itself

Abstract

Soluble γ-secretase modulators (SGSMs) selectively decrease toxic amyloid β (Aβ) peptides (Aβ42). However, their effect on the physiologic functions of γ-secretase has not been tested in human model systems. γ-Secretase regulates fate determination of neural progenitor cells. Thus, we studied the impact of SGSMs on the neuronal differentiation of ReNcell VM (ReN) human neural progenitor cells (hNPCs). Quantitative PCR analysis showed that treatment of neurosphere-like ReN cell aggregate cultures with γ-secretase inhibitors (GSIs), but not SGSMs, induced a 2- to 4-fold increase in the expression of the neuronal markers Tuj1 and doublecortin. GSI treatment also induced neuronal marker protein expression, as shown by Western blot analysis. In the same conditions, SGSM treatment selectively reduced endogenous Aβ42 levels by ∼80%. Mechanistically, we found that Notch target gene expressions were selectively inhibited by a GSI, not by SGSM treatment. We can assert, for the first time, that SGSMs do not affect the neuronal differentiation of hNPCs while selectively decreasing endogenous Aβ42 levels in the same conditions. Our results suggest that our hNPC differentiation system can serve as a useful model to test the impact of GSIs and SGSMs on both endogenous Aβ levels and γ-secretase physiologic functions including endogenous Notch signaling.

Indexed as

Amyloid beta-PeptidesAmyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesCell DifferentiationCells, CulturedDoublecortin Domain ProteinsHumansMicrotubule-Associated ProteinsNeural Stem CellsNeuronsNeuropeptidesPeptide FragmentsSignal TransductionTubulinAmyloid beta-Peptidesamyloid beta-protein (10-43)Amyloid beta-Protein PrecursorAmyloid Precursor Protein SecretasesDoublecortin Domain ProteinsMicrotubule-Associated ProteinsNeuropeptidesPeptide FragmentsTUBB3 protein, humanTubulinAlzheimer’s diseaseNotchpresenilinReNcell VMSGSM

Identifiers

PMID25903103
PMCPMC4511200

What OpenQuestion holds

Textmetadata
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 OpenQuestion graph.