ArticleMolecular therapy : the journal of the American Society of Gene Therapy2023
Intravenous treatment with a molecular chaperone designed against β-amyloid toxicity improves Alzheimer's disease pathology in mouse models.
Article in Molecular therapy : the journal of the American Society of Gene Therapy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 33 citations in OpenAlex.
- Mechanism-selective inhibition of α-synuclein aggregation by the chaperone-like BRICHOS domain.The Journal of biological chemistry · 2026Article
- Chaperone-Mediated Regulation of Tau Phase Separation, Fibrillation, and Toxicity.Journal of the American Chemical Society · 2025Article
- Determinants for Substoichiometric Inhibition of IAPP and Aβ Amyloid Aggregations by Bri2 BRICHOS.ACS chemical neuroscience · 2025Article
- Intraneuronal Aβ accumulation causes tau hyperphosphorylation via endolysosomal leakage.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- The inhibitory action of the chaperone BRICHOS against the α-Synuclein secondary nucleation pathway.Nature communications · 2024Article
- Potential of molecular chaperones for treating Alzheimer's disease.Neural regeneration research · 2024Article
- Intravenous chaperone treatment of late-stage Alzheimer´s disease (AD) mouse model affects amyloid plaque load, reactive gliosis and AD-related genes.Translational psychiatry · 2024Article
- Specific inhibition of α-synuclein oligomer generation and toxicity by the chaperone domain Bri2 BRICHOS.Protein science : a publication of the Protein Society · 2024Article
- Molecular basis for different substrate-binding sites and chaperone functions of the BRICHOS domain.Protein science : a publication of the Protein Society · 2024Article
- Reply to Johansson 'Treatment with BRICHOS domain helps to clarify issues with Alzheimer mouse models'.EMBO molecular medicine · 2024Article
- Treatment with BRICHOS domain helps to clarify issues with Alzheimer mouse models.EMBO molecular medicine · 2024Article
- Functional BRI2-TREM2 interactions in microglia: implications for Alzheimer's and related dementias.EMBO reports · 2024Article
- Myelin Basic Protein Attenuates Furin-Mediated Bri2 Cleavage and Postpones Its Membrane Trafficking.International journal of molecular sciences · 2024Article
- Identification of potential aggregation hotspots on Aβ42 fibrils blocked by the anti-amyloid chaperone-like BRICHOS domain.Nature communications · 2024Article
- Updates on Aβ Processing by Hsp90, BRICHOS, and Newly Reported Distinctive Chaperones.Biomolecules · 2023Review
- Metal Binding of Alzheimer's Amyloid-β and Its Effect on Peptide Self-Assembly.Accounts of chemical research · 2023Article
- Identification of glycolytic proteins as binding partners of Bri2 BRICHOS domain.Journal of pharmaceutical and biomedical analysis · 2023Article
- A new kid in the folding funnel: Molecular chaperone activities of the BRICHOS domain.Protein science : a publication of the Protein Society · 2023Review
- Amyloid inhibition by molecular chaperonesRSC medicinal chemistry · 2023Review
- Molecular Mechanisms of Amyloid-β Self-Assembly Seeded by In Vivo-Derived Fibrils and Inhibitory Effects of the BRICHOS Chaperone.ACS chemical neuroscience · 2023Article
Corrections and comments
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Attempts to treat Alzheimer's disease with immunotherapy against the β-amyloid (Aβ) peptide or with enzyme inhibitors to reduce Aβ production have not yet resulted in effective treatment, suggesting that alternative strategies may be useful. Here we explore the possibility of targeting the toxicity associated with Aβ aggregation by using the recombinant human (rh) Bri2 BRICHOS chaperone domain, mutated to act selectively against Aβ42 oligomer generation and neurotoxicity in vitro. We find that treatment of Aβ precursor protein (App) knockin mice with repeated intravenous injections of rh Bri2 BRICHOS R221E, from an age close to the start of development of Alzheimer's disease-like pathology, improves recognition and working memory, as assessed using novel object recognition and Y maze tests, and reduces Aβ plaque deposition and activation of astrocytes and microglia. When treatment was started about 4 months after Alzheimer's disease-like pathology was already established, memory improvement was not detected, but Aβ plaque deposition and gliosis were reduced, and substantially reduced astrocyte accumulation in the vicinity of Aβ plaques was observed. The degrees of treatment effects observed in the App knockin mouse models apparently correlate with the amounts of Bri2 BRICHOS detected in brain sections after the end of the treatment period.
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