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

γ-Secretase modulator resistance of an aggressive Alzheimer-causing presenilin mutant can be overcome in the heterozygous patient state by a set of advanced compounds.

Alzheimer's research & therapy - 19 Feb 2025

Trambauer Johannes, Sarmiento Rosa Maria Rodriguez, Garringer Holly J, Salbaum Katja, Pedro Liliana D, Crusius Dennis, Vidal Ruben, Ghetti Bernardino, Paquet Dominik, Baumann Karlheinz, Lindemann Lothar, Steiner Harald

Abstract excerpt

BACKGROUND: Amyloid-β peptide (Aβ) species of 42 or 43 amino acids in length (Aβ42/43) trigger Alzheimer´s disease (AD) and are produced in abnormal amounts by mutants of the γ-secretase subunit presenilin-1 (PS1), which represent the primary cause of familial AD (FAD). Lowering these peptides by γ-secretase modulators (GSMs) is increasingly considered a safe strategy to treat AD since these compounds do not...

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 Precursor Protein Secretases

Share to Fibroblasts

Share to Heterozygote

Share to Induced Pluripotent Stem Cells

Share to Peptide Fragments

Share to Presenilin-1

Source

Open in PubMed Open full text

Identifiers

PMID: 39972463
DOI: 10.1186/s13195-025-01680-3
PMCID: PMC11837686

Provenance

PubMed metadata and Literature Corpus relationships. Corpus snapshot updated 7 Sept 2026.

Related research

Semantic proximity does not establish scientific evidence.

Research trail→

Click a neighbor to travelStep 1 · 12 closest

γ-Secretase modulator resistance of an aggressive Alzheimer-causing presenilin mutant can be overcome in the heterozygous patient state by a set of advanced compounds.PMID 39972463Read ↗

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

Aβ43-producing PS1 FAD mutants cause altered substrate interactions and respond to γ-secretase modulation.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 ↗

Attenuated Abeta42 responses to low potency gamma-secretase modulators can be overcome for many pathogenic presenilin mutants by second-generation compounds.Semantic proximity Read ↗

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

Characterization of intermediate steps in amyloid beta (Aβ) production under near-native conditions.Semantic proximity Read ↗

Soluble γ-secretase modulators selectively inhibit the production of the 42-amino acid amyloid β peptide variant and augment the production of multiple carboxy-truncated amyloid β species.Semantic proximity Read ↗

Suppressor Mutations for Presenilin 1 Familial Alzheimer Disease Mutants Modulate γ-Secretase Activities.Semantic proximity Read ↗

Effect of potent γ-secretase modulator in human neurons derived from multiple presenilin 1-induced pluripotent stem cell mutant carriers.Semantic proximity Read ↗

Alzheimer's Disease: Presenilin 2-Sparing γ-Secretase Inhibition Is a Tolerable Aβ Peptide-Lowering StrategySemantic proximity Read ↗

Pathogenic Aβ generation in familial Alzheimer's disease: novel mechanistic insights and therapeutic implications.Semantic proximity Read ↗

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