ArticleCell reports2017
CRISPR Transcriptional Activation Analysis Unmasks an Occult γ-Secretase Processivity Defect in Familial Alzheimer's Disease Skin Fibroblasts.
Article in Cell reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
What it found
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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.
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Who cites it
10 citing papers in PubMed, 21 citations in OpenAlex.
- Screening Techniques for Drug Discovery in Alzheimer's Disease.ACS omega · 2024Review
- CRISPR and iPSCs: Recent Developments and Future Perspectives in Neurodegenerative Disease Modelling, Research, and Therapeutics.Neurotoxicity research · 2022Review
- Delivering the Promise of Gene Therapy with Nanomedicines in Treating Central Nervous System Diseases.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2022Review
- Article
- Gene Editing and Alzheimer's Disease: Is There Light at the End of the Tunnel?Frontiers in genome editing · 2020Review
- Plasma biomarkers of the amyloid pathway are associated with geographic atrophy secondary to age-related macular degeneration.PloS one · 2020Article
- Targeted DNA methylation of neurodegenerative disease genes via homology directed repair.Nucleic acids research · 2019Article
- Next Generation Precision Medicine: CRISPR-mediated Genome Editing for the Treatment of Neurodegenerative Disorders.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2019Review
- Article
- Alzheimer disease: CRISPR activation reveals hidden γ-secretase defect in fibroblasts from patients with familial AD.Nature reviews. Neurology · 2018Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
Mutations in presenilin (PSEN) 1 and 2, which encode components of the γ-secretase (GS) complex, cause familial Alzheimer's disease (FAD). It is hypothesized that altered GS-mediated processing of the amyloid precursor protein (APP) to the Aβ42 fragment, which is accumulated in diseased brain, may be pathogenic. Here, we describe an in vitro model system that enables the facile analysis of neuronal disease mechanisms in non-neuronal patient cells using CRISPR gene activation of endogenous disease-relevant genes. In FAD patient-derived fibroblast cultures, CRISPR activation of APP or BACE unmasked an occult processivity defect in downstream GS-mediated carboxypeptidase cleavage of APP, ultimately leading to higher Aβ42 levels. These data suggest that, selectively in neurons, relatively high levels of BACE1 activity lead to substrate pressure on FAD-mutant GS complexes, promoting CNS Aβ42 accumulation. Our results introduce an additional platform for analysis of neurological disease.
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Registered trials
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.