ArticleNeurobiology of disease2015
Novel therapeutic strategy for neurodegeneration by blocking Aβ seeding mediated aggregation in models of Alzheimer's disease.
Article in Neurobiology of disease, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers, 1 of them a synthesis that pooled it.
What it found
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
16 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- Intestinal Flora Balance Therapy Based on Probiotic Support Improves Cognitive Function and Symptoms in Patients with Alzheimer's Disease: A Systematic Review and Meta-analysis.BioMed research international · 2022Pooled it
- Lack of cellular prion protein causes Amyloid β accumulation, increased extracellular vesicle abundance, and changes to exosome biogenesis proteins.Molecular and cellular biochemistry · 2025Article
- Bithionol eliminates acute myeloid leukaemia stem-like cells by suppressing NF-κB signalling and inducing oxidative stress, leading to apoptosis and ferroptosis.Cell death discovery · 2024Article
- Negative modulation of mitochondrial calcium uniporter complex protects neurons against ferroptosis.Cell death & disease · 2023Article
- Integrating Comorbidity Knowledge for Alzheimer's Disease Drug Repurposing using Multi-task Graph Neural Network.AMIA Joint Summits on Translational Science proceedings. AMIA Joint Summits on Translational Science · 2023Article
- A reaction-diffusion model of spatial propagation of AJournal of mathematical biology · 2021Article
- Drug Repurposing for Alzheimer's Disease Based on Protein-Protein Interaction Network.BioMed research international · 2021Article
- The Full Spectrum of Alzheimer's Disease Is Rooted in Metabolic Derangements That Drive Type 3 Diabetes.Advances in experimental medicine and biology · 2019Review
- Review
- Therapeutic Approaches for Zika Virus Infection of the Nervous System.Neurotherapeutics : the journal of the American Society for Experimental NeuroTherapeutics · 2017Review
- Seed-induced acceleration of amyloid-β mediated neurotoxicity in vivo.Nature communications · 2017Article
- Pituitary adenylate cyclase-activating polypeptide (PACAP) protects against mitoxantrone-induced cardiac injury in mice.Peptides · 2017Article
- A de novo compound targeting α-synuclein improves deficits in models of Parkinson's disease.Brain : a journal of neurology · 2016Article
- Bithionol blocks pathogenicity of bacterial toxins, ricin, and Zika virus.Scientific reports · 2016Article
- Blocking mPTP on Neural Stem Cells and Activating the Nicotinic Acetylcholine Receptor α7 Subunit on Microglia Attenuate Aβ-Induced Neurotoxicity on Neural Stem Cells.Neurochemical research · 2016Article
- Targeting protein aggregation for the treatment of degenerative diseases.Nature reviews. Drug discovery · 2015Review
Corrections and comments
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Authors and funding
11 authors at 2 institutions in 2 countries.
Funding
Abstract
Aβ accumulation plays a central role in the pathogenesis of Alzheimer's disease (AD). Recent studies suggest that the process of Aβ nucleated polymerization is essential for Aβ fibril formation, pathology spreading and toxicity. Therefore, targeting this process represents an effective therapeutic strategy to slow or block disease progression. To discover compounds that might interfere with the Aβ seeding capacity, toxicity and pathology spreading, we screened a focused library of FDA-approved drugs in vitro using a seeding polymerization assay and identified small molecule inhibitors that specifically interfered with Aβ seeding-mediated fibril growth and toxicity. Mitoxantrone, bithionol and hexachlorophene were found to be the strongest inhibitors of fibril growth and protected primary cortical neuronal cultures against Aβ-induced toxicity. Next, we assessed the effects of these three inhibitors in vivo in the mThy1-APPtg mouse model of AD (8-month-old mice). We found that mitoxantrone and bithionol, but not hexachlorophene, stabilized diffuse amyloid plaques, reduced the levels of Aβ42 oligomers and ameliorated synapse loss, neuronal damage and astrogliosis. Together, our findings suggest that targeting fibril growth and Aβ seeding capacity constitutes a viable and effective strategy for protecting against neurodegeneration and disease progression in AD.
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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.