Evidence mapPaperPMID 40927393Full record

ReviewFrontiers in aging neuroscience2025

The manipulator behind "Scissors": γ -secretase and its modulators in Alzheimer's disease.

Gao Ning, Xing Fan, Du Juan, Zhao Wenxue, Wang Sijia, Chen Meinei, Dong Xiaolong, Qi Yiming

Abstract readReview
In one paragraph

Review in Frontiers in aging neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing 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

5 citing papers in PubMed.

  1. Review
  2. Review
  3. Review
  4. Review
  5. 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

8 authors.

Gao Ning *Yan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.
Xing Fan *Yan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.
Du JuanYan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.
Zhao WenxueYan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.
Wang SijiaYan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.
Chen MeineiYan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.
Dong XiaolongYan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.
Qi YimingYan'an Medical College of Yan'an University, Yan'an, Shaanxi, China.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

The intramembrane aspartic protease, γ-secretase, is a heterotetrameric protein complex composed of four integral membrane proteins: presenilin (PSEN), nicastrin (NCT), Anterior pharynx defective-1 (APH-1), and presenilin enhancer 2 (PEN-2). These components are sequentially assembled into a functional complex. γ-secretase is ubiquitously expressed in all cells and tissues and exhibits enzymatic activity akin to "molecular scissors" by cleaving various type I transmembrane proteins. The primary substrates of this complex include amyloid precursor protein (APP) and Notch. The role of APP in the pathogenesis of Alzheimer's disease (AD) has been extensively investigated. Although γ-secretase inhibitors (GSIs) have been evaluated for their therapeutic potential in AD, their clinical application is limited due to significant toxic side effects. Recently, γ-secretase modulators (GSMs) have emerged as promising alternatives, offering new opportunities for the treatment of AD, especially the inherent γ-secretase modulatory proteins (GSMPs) within cells. Research on GSMPs has ushered in a new era for mitigating the side effects of AD drugs. In this review, we systematically summarize recent advancements in the study of γ-secretase in relation to AD and provide an overview of GSMs and GSMPs, thereby offering potential insights for the development of therapeutic strategies for AD.

Indexed as

Alzheimer’s diseaseGSMPsGSMStype I transmembrane proteinsγ-secretase

Identifiers

PMID40927393
PMCPMC12414960

What Socratic holds

Textmetadata
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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.