ArticleScientific reports2016
Tackling amyloidogenesis in Alzheimer's disease with A2V variants of Amyloid-β.
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 18 papers.
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Who cites it
18 citing papers in PubMed, 31 citations in OpenAlex.
- Designed Cell-Penetrating Peptide Constructs for Inhibition of Pathogenic Protein Self-Assembly.Pharmaceutics · 2024Review
- Functionalized nanoparticles to deliver nucleic acids to the brain for the treatment of Alzheimer's disease.Frontiers in pharmacology · 2024Review
- Aβ1-6Molecular psychiatry · 2023Article
- Targeting Protein-Protein Interfaces with Peptides: The Contribution of Chemical Combinatorial Peptide Library Approaches.International journal of molecular sciences · 2023Review
- A novel bio-inspired strategy to prevent amyloidogenesis and synaptic damage in Alzheimer's disease.Molecular psychiatry · 2022Article
- Overcoming the cellular barriers and beyond: Recent progress on cell penetrating peptide modified nanomedicine in combating physiological and pathological barriers.Asian journal of pharmaceutical sciences · 2022Review
- Serpin Signatures in Prion and Alzheimer's Diseases.Molecular neurobiology · 2022Article
- Combination of cell-penetrating peptides with nanomaterials for the potential therapeutics of central nervous system disorders: a review.Journal of nanobiotechnology · 2021Review
- Gene therapy using Aβ variants for amyloid reduction.Molecular therapy : the journal of the American Society of Gene Therapy · 2021Article
- Contributions of Mass Spectrometry to the Identification of Low Molecular Weight Molecules Able to Reduce the Toxicity of Amyloid-β Peptide to Cell Cultures and Transgenic Mouse Models of Alzheimer's Disease.Molecules (Basel, Switzerland) · 2019Review
- Review of Current Strategies for Delivering Alzheimer's Disease Drugs across the Blood-Brain Barrier.International journal of molecular sciences · 2019Review
- Dreaming of a New World Where Alzheimer's Is a Treatable Disorder.Frontiers in aging neuroscience · 2019Article
- Looking at the Disordered Proteins through the Computational Microscope.ACS central science · 2018Review
- New Insights on the Role of Residue 673 of APP in Alzheimer's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- Translational Research in Alzheimer's and Prion Diseases.Journal of Alzheimer's disease : JAD · 2018Review
- Emergence of Alternative Structures in Amyloid Beta 1-42 Monomeric Landscape by N-terminal Hexapeptide Amyloid Inhibitors.Scientific reports · 2017Article
- The A2V mutation as a new tool for hindering Aβ aggregation: A neutron and x-ray diffraction study.Scientific reports · 2017Article
- Self-assembly of the full-length amyloid Aβ42 protein in dimers.Nanoscale · 2016Article
Corrections and comments
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Authors and funding
18 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
We developed a novel therapeutic strategy for Alzheimer's disease (AD) exploiting the properties of a natural variant of Amyloid-β (Aβ) carrying the A2V substitution, which protects heterozygous carriers from AD by its ability to interact with wild-type Aβ, hindering conformational changes and assembly thereof. As prototypic compound we designed a six-mer mutated peptide (Aβ1-6A2V), linked to the HIV-related TAT protein, which is widely used for brain delivery and cell membrane penetration of drugs. The resulting molecule [Aβ1-6A2VTAT(D)] revealed strong anti-amyloidogenic effects in vitro and protected human neuroblastoma cells from Aβ toxicity. Preclinical studies in AD mouse models showed that short-term treatment with Aβ1-6A2VTAT(D) inhibits Aβ aggregation and cerebral amyloid deposition, but a long treatment schedule unexpectedly increases amyloid burden, although preventing cognitive deterioration. Our data support the view that the AβA2V-based strategy can be successfully used for the development of treatments for AD, as suggested by the natural protection against the disease in human A2V heterozygous carriers. The undesirable outcome of the prolonged treatment with Aβ1-6A2VTAT(D) was likely due to the TAT intrinsic attitude to increase Aβ production, avidly bind amyloid and boost its seeding activity, warning against the use of the TAT carrier in the design of AD therapeutics.
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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.