ArticleScientific reports2017
A Toxic Conformer of Aβ42 with a Turn at 22-23 is a Novel Therapeutic Target for Alzheimer's Disease.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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14 citing papers in PubMed, 27 citations in OpenAlex.
- A Blood-Brain Barrier-Penetrant Ag(III) Corrole Compound Rescues Alzheimer's Disease Pathology by Targeting Aβ42-Induced Oxidative Stress.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Aducanumab binds high molecular weight soluble Aβ oligomers and restores intracellular calcium levels.Alzheimer's research & therapy · 2025Article
- Sequence-based identification of amyloidogenic β-hairpins reveals a prostatic acid phosphatase fragment promoting semen amyloid formation.Computational and structural biotechnology journal · 2024Article
- Nucleation of α-Synuclein Amyloid Fibrils Induced by Cross-Interaction with β-Hairpin Peptides Derived from Immunoglobulin Light Chains.International journal of molecular sciences · 2023Article
- Insulin resistance induces earlier initiation of cognitive dysfunction mediated by cholinergic deregulation in a mouse model of Alzheimer's disease.Aging cell · 2023Article
- APP Knock-In Mice Produce E22P-Aβ Exhibiting an Alzheimer's Disease-like Phenotype with Dysregulation of Hypoxia-Inducible Factor Expression.International journal of molecular sciences · 2022Article
- Shati/Nat8l Overexpression Improves Cognitive Decline by Upregulating Neuronal Trophic Factor in Alzheimer's Disease Model Mice.Neurochemical research · 2022Article
- Knockdown of Piccolo in the Nucleus Accumbens Suppresses Methamphetamine-Induced Hyperlocomotion and Conditioned Place Preference in Mice.Neurochemical research · 2022Article
- Understanding and controlling amyloid aggregation with chirality.Current opinion in chemical biology · 2021Review
- New Insights Regarding Diagnosis and Medication for Schizophrenia Based on Neuronal Synapse-Microglia Interaction.Journal of personalized medicine · 2021Review
- A Mechanistic Evaluation of Antioxidant Nutraceuticals on Their Potential against Age-Associated Neurodegenerative Diseases.Antioxidants (Basel, Switzerland) · 2020Review
- Risk of developing cerebral β-amyloid plaques with posttranslational modification among HIV-infected adults.AIDS (London, England) · 2019Article
- The Mode of Action of an Anti-Oligomeric Amyloid β-Protein Antibody Affects its Protective Efficacy.Neurotoxicity research · 2019Article
- Change of Amyloid-β 1-42 Toxic Conformer Ratio After Cerebrospinal Fluid Diversion Predicts Long-Term Cognitive Outcome in Patients with Idiopathic Normal Pressure Hydrocephalus.Journal of Alzheimer's disease : JAD · 2018Observational
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Immunotherapy targeting Aβ42 is drawing attention as a possible therapeutic approach for Alzheimer's disease (AD). Considering the significance of reported oligomerized Aβ42 species, selective targeting of the oligomer will increase the therapeutic efficacy. However, what kinds of oligomers are suitable targets for immunotherapy remains unclear. We previously identified a toxic conformer of Aβ42, which has a turn structure at 22-23 ("toxic turn"), among Aβ42 conformations. This toxic conformer of Aβ42 has been reported to show rapid oligomerization and to exhibit strong neurotoxicity and synaptotoxicity. We recently developed a monoclonal antibody against the toxic conformer (24B3), which demonstrated the increase of the toxic conformer in the cerebrospinal fluid of AD patients, indicating its accumulation in AD patients' brains. In this study, we evaluated the therapeutic efficacy of 24B3 targeting the toxic conformer in AD model mice. The intraperitoneal administration of 24B3 for 3 months improved cognitive impairment and reduced the toxic conformer levels. Notably, this treatment did not reduce the number of senile plaques. Furthermore, the single intravenous administration of 24B3 suppressed the memory deficit in AD mice. These results suggest that the toxic conformer of Aβ42 with a turn at 22-23 represents one of the promising therapeutic targets.
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