Discover Community Create You

Loading publication...

Noodle always counts identifier-free feature events for service operation. With your permission, Google Analytics can also estimate audience and engagement. Search text, publication identifiers, cookies, IP addresses and browser fingerprints are never included in Noodle's first-party event counters.

Privacy details

Article

Hydrophilic loop 1 of Presenilin-1 and the APP GxxxG transmembrane motif regulate γ-secretase function in generating Alzheimer-causing Aβ peptides.

The Journal of biological chemistry - 1 Jan 2000

Liu Lei, Lauro Bianca M, Wolfe Michael S, Selkoe Dennis J

Abstract excerpt

γ-Secretase is responsible for the proteolysis of amyloid precursor protein (APP) into amyloid-beta (Aβ) peptides, which are centrally implicated in the pathogenesis of Alzheimer's disease (AD). The biochemical mechanism of how processing by γ-secretase is regulated, especially as regards the interaction between enzyme and substrate, remains largely unknown. Here, mutagenesis reveals that the hydrophilic loop-1...

Read the complete abstract on PubMed

Topics

Share this publication in a Topic to start or enrich a Post.

Share to Alzheimer Disease
Share to Amyloid beta-Peptides

Methodology Data sources Editorial policy Privacy About Contact Helena Bioinformatics

Share to Amyloid beta-Protein Precursor

Share to Amyloid Precursor Protein Secretases

Share to Presenilin-1

Share to Protein Domains

Share to Proteolysis

Share to Substrate Specificity

Source

Open in PubMed Open full text

Identifiers

PMID: 33571524
DOI: 10.1016/j.jbc.2021.100393
PMCID: PMC7961089

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026. Manifest publication-graph-cohort-2026-09-07.1.

Source receipt: pubmed, retrieved 7 Sept 2026.

Related research

Semantic proximity does not establish scientific evidence.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

Hydrophilic loop 1 of Presenilin-1 and the APP GxxxG transmembrane motif regulate γ-secretase function in generating Alzheimer-causing Aβ peptides.PMID 33571524Read ↗

Important functional role of residue x of the presenilin GxGD protease active site motif for APP substrate cleavage specificity and substrate selectivity of γ-secretase.Semantic proximity Read ↗

Dynamic Nature of presenilin1/γ-Secretase: Implication for Alzheimer's Disease Pathogenesis.Semantic proximity Read ↗

Alzheimer presenilin-1 mutations dramatically reduce trimming of long amyloid β-peptides (Aβ) by γ-secretase to increase 42-to-40-residue Aβ.Semantic proximity Read ↗

Mutation analysis of the presenilin 1 N-terminal domain reveals a broad spectrum of gamma-secretase activity toward amyloid precursor protein and other substrates.Semantic proximity Read ↗

Presenilin-1 but not amyloid precursor protein mutations present in mouse models of Alzheimer's disease attenuate the response of cultured cells to γ-secretase modulators regardless of their potency and structure.Semantic proximity Read ↗

Requirement for small side chain residues within the GxGD-motif of presenilin for gamma-secretase substrate cleavage.Semantic proximity Read ↗

Conformational Changes in Transmembrane Domain 4 of Presenilin 1 Are Associated with Altered Amyloid-β 42 Production.Semantic proximity Read ↗

Characterization of FRM-36143 as a new γ-secretase modulator for the potential treatment of familial Alzheimer's disease.Semantic proximity Read ↗

Activation of γ-Secretase Trimming Activity by Topological Changes of Transmembrane Domain 1 of Presenilin 1.Semantic proximity Read ↗

Presenilin, γ-Secretase, and the Search for Pathogenic Triggers of Alzheimer's Disease.Semantic proximity Read ↗

Two Novel Mutations in the First Transmembrane Domain of Presenilin1 Cause Young-Onset Alzheimer's Disease.Semantic proximity Read ↗

APP substrate ectodomain defines Aβ length by restraining γ-secretase processivity and facilitating product releaseSemantic proximity Read ↗

⌁Select a neighboring publication to make it the new centre.