ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
The prion protein ligand, stress-inducible phosphoprotein 1, regulates amyloid-β oligomer toxicity.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 45 papers.
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Who cites it
45 citing papers in PubMed, 83 citations in OpenAlex.
- A phase separation hypothesis for the biological function of PrP: the role of multivalent interactions at the plasma membrane.Biochemical Society transactions · 2026Review
- Prefoldin 5 is a microtubule-associated protein that suppresses Tau aggregation and neurotoxicity.eLife · 2026Article
- Disease-associated RNA and protein signatures in iPSC-derived microglia model of Alzheimer's disease.Frontiers in neuroscience · 2026Article
- A Longitudinal Study of Sex Differences in a TDP-43 Mouse Model Reveals STI1 Regulation of TDP-43 Proteinopathy and Motor Deficits.Journal of neurochemistry · 2025Article
- The role of the FKBP51-Hsp90 complex in Alzheimer's disease: An emerging new drug target.Cell stress & chaperones · 2024Review
- Chaperones-A New Class of Potential Therapeutic Targets in Alzheimer's Disease.International journal of molecular sciences · 2024Review
- Blood RNA transcripts reveal similar and differential alterations in fundamental cellular processes in Alzheimer's disease and other neurodegenerative diseases.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2023Article
- Stress-inducible phosphoprotein 1 (HOP/STI1/STIP1) regulates the accumulation and toxicity of α-synuclein in vivo.Acta neuropathologica · 2022Article
- Parkinson's Disease-Specific Autoantibodies against the Neuroprotective Co-Chaperone STIP1.Cells · 2022Article
- The Hsp70-Hsp90 go-between Hop/Stip1/Sti1 is a proteostatic switch and may be a drug target in cancer and neurodegeneration.Cellular and molecular life sciences : CMLS · 2021Review
- Stress-induced phosphoprotein 1 restrains spinal cord ischaemia-reperfusion injury by modulating NF-κB signalling.Journal of cellular and molecular medicine · 2021Article
- Review
- Altered cellular localisation and expression, together with unconventional protein trafficking, of prion protein, PrPDiabetologia · 2021Article
- Review
- Protein S-nitrosylation and oxidation contribute to protein misfolding in neurodegeneration.Free radical biology & medicine · 2021Review
- Tau Exon 10 Inclusion by PrPInternational journal of molecular sciences · 2021Article
- The Cellular Prion Protein: A Promising Therapeutic Target for Cancer.International journal of molecular sciences · 2020Review
- Cellular Prion Protein (PrPc): Putative Interacting Partners and Consequences of the Interaction.International journal of molecular sciences · 2020Review
- Increased levels of Stress-inducible phosphoprotein-1 accelerates amyloid-β deposition in a mouse model of Alzheimer's disease.Acta neuropathologica communications · 2020Article
- Show Me Your Friends and I Tell You Who You Are: The Many Facets of Prion Protein in Stroke.Cells · 2020Review
Corrections and comments
- Erratum issued
Authors and funding
21 authors at 7 institutions in 5 countries.
Funding
Abstract
In Alzheimer's disease (AD), soluble amyloid-β oligomers (AβOs) trigger neurotoxic signaling, at least partially, via the cellular prion protein (PrP(C)). However, it is unknown whether other ligands of PrP(C) can regulate this potentially toxic interaction. Stress-inducible phosphoprotein 1 (STI1), an Hsp90 cochaperone secreted by astrocytes, binds to PrP(C) in the vicinity of the AβO binding site to protect neurons against toxic stimuli. Here, we investigated a potential role of STI1 in AβO toxicity. We confirmed the specific binding of AβOs and STI1 to the PrP and showed that STI1 efficiently inhibited AβO binding to PrP in vitro (IC50 of ∼70 nm) and also decreased AβO binding to cultured mouse primary hippocampal neurons. Treatment with STI1 prevented AβO-induced synaptic loss and neuronal death in mouse cultured neurons and long-term potentiation inhibition in mouse hippocampal slices. Interestingly, STI1-haploinsufficient neurons were more sensitive to AβO-induced cell death and could be rescued by treatment with recombinant STI1. Noteworthy, both AβO binding to PrP(C) and PrP(C)-dependent AβO toxicity were inhibited by TPR2A, the PrP(C)-interacting domain of STI1. Additionally, PrP(C)-STI1 engagement activated α7 nicotinic acetylcholine receptors, which participated in neuroprotection against AβO-induced toxicity. We found an age-dependent upregulation of cortical STI1 in the APPswe/PS1dE9 mouse model of AD and in the brains of AD-affected individuals, suggesting a compensatory response. Our findings reveal a previously unrecognized role of the PrP(C) ligand STI1 in protecting neurons in AD and suggest a novel pathway that may help to offset AβO-induced toxicity.
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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.