ArticleScientific reports2016
Aβ42 oligomers modulate β-secretase through an XBP-1s-dependent pathway involving HRD1.
Article in Scientific reports, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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Who cites it
15 citing papers in PubMed, 24 citations in OpenAlex.
- Adaptive-to-maladaptive IRE1α signaling as a driver of amyloidogenic APP processing in Alzheimer's disease.Frontiers in molecular biosciences · 2026Review
- Roles of Ubiquitin Ligases and Deubiquitylases in Alzheimer's Disease.Molecular neurobiology · 2025Review
- The ubiquitin-proteasome system in Alzheimer's disease: mechanism of action and current status of treatment.Frontiers in aging neuroscience · 2025Review
- Involvement of ubiquitination in Alzheimer's disease.Frontiers in neurology · 2024Review
- The unfolded protein response transcription factor XBP1s ameliorates Alzheimer's disease by improving synaptic function and proteostasis.Molecular therapy : the journal of the American Society of Gene Therapy · 2023Article
- Review
- EDEM1 Regulates Amyloid Precursor Protein (APP) Metabolism and Amyloid-β Production.International journal of molecular sciences · 2021Article
- Article
- Roles of XBP1s in Transcriptional Regulation of Target Genes.Biomedicines · 2021Review
- Review
- Molecular Dysfunctions of Mitochondria-Associated Membranes (MAMs) in Alzheimer's Disease.International journal of molecular sciences · 2020Review
- Alterations of the Endoplasmic Reticulum (ER) Calcium Signaling Molecular Components in Alzheimer's Disease.Cells · 2020Review
- Exploring the Promise of Targeting Ubiquitin-Proteasome System to Combat Alzheimer's Disease.Neurotoxicity research · 2020Review
- Article
- The transcription factor XBP1 in memory and cognition: Implications in Alzheimer disease.Molecular medicine (Cambridge, Mass.) · 2017Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The aspartyl protease β-site APP cleaving enzyme, BACE1, is the rate-limiting enzyme involved in the production of amyloid-β peptide, which accumulates in both sporadic and familial cases of Alzheimer's disease and is at the center of gravity of the amyloid cascade hypothesis. In this context, unravelling the molecular mechanisms controlling BACE1 expression and activity in both physiological and pathological conditions remains of major importance. We previously demonstrated that Aβ controlled BACE1 transcription in an NFκB-dependent manner. Here, we delineate an additional cellular pathway by which natural and synthetic Aβ42 oligomers enhance active X-box binding protein XBP-1s. XBP-1s lowers BACE1 expression and activity indirectly, via the up-regulation of the ubiquitin-ligase HRD1 that acts as an endogenous down-regulator of BACE1. Thus, we delineate a novel pathway by which cells could compensate for Aβ42 oligomers production and thus, associated toxicity, by triggering a compensatory mechanism aimed at lowering BACE-1-mediated Aβ production by a molecular cascade involving XBP-1s and HRD1. It thus identifies HRD1 as a potential target for a novel Aβ-centered therapeutic strategy.
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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.