ArticleProceedings of the National Academy of Sciences of the United States of America2009
Small molecule blockers of the Alzheimer Abeta calcium channel potently protect neurons from Abeta cytotoxicity.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 52 papers.
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Who cites it
52 citing papers in PubMed, 114 citations in OpenAlex.
- Review
- Decoding the mechanisms of amyloid-β in synaptic toxicity.Journal of Alzheimer's disease : JAD · 2026Review
- Connexin 43 Role in Mitochondrial Transfer and Homeostasis in the Central Nervous System.Journal of cellular physiology · 2025Review
- The structure of tyrosine-10 favors ionic conductance of Alzheimer's disease-associated full-length amyloid-β channels.Nature communications · 2024Article
- Review
- Chronic Administration of Ion Channel Blockers Impact Microglia Morphology and Function in a Murine Model of Alzheimer's Disease.International journal of molecular sciences · 2023Article
- Quantitative Attribution of the Protective Effects of Aminosterols against Protein Aggregates to Their Chemical Structures and Ability to Modulate Biological Membranes.Journal of medicinal chemistry · 2023Article
- Endogenous Amyloid-formed CaFunction (Oxford, England) · 2023Article
- Stereospecific antiseizure activity in mouse and rat epilepsy models by a pyridinium inhibitor of TNFα/NFκB signaling.European journal of medicinal chemistry reports · 2022Article
- Misfolded protein oligomers induce an increase of intracellular CaCellular and molecular life sciences : CMLS · 2022Article
- Exposure of metal toxicity in Alzheimer's disease: An extensive review.Frontiers in pharmacology · 2022Review
- The Stimulatory Effects of Intracellular α-Synuclein on Synaptic Transmission Are Attenuated by 2-Octahydroisoquinolin-2(1H)-ylethanamine.International journal of molecular sciences · 2021Article
- Prediction of Transmembrane Regions, Cholesterol, and Ganglioside Binding Sites in Amyloid-Forming Proteins Indicate Potential for Amyloid Pore Formation.Frontiers in molecular neuroscience · 2021Article
- Molecular Mechanisms of Metal Toxicity in the Pathogenesis of Alzheimer's Disease.Molecular neurobiology · 2021Review
- Review
- Hexahydropyrrolo[2,3-ACS chemical neuroscience · 2019Article
- Photoactive chlorin e6 is a multifunctional modulator of amyloid-β aggregation and toxicityChemical science · 2019Article
- N-Terminal Charged Residues of Amyloid-β Peptide Modulate Amyloidogenesis and Interaction with Lipid Membrane.Chemistry (Weinheim an der Bergstrasse, Germany) · 2018Article
- The diphenylpyrazole compound anle138b blocks Aβ channels and rescues disease phenotypes in a mouse model for amyloid pathology.EMBO molecular medicine · 2018Article
- Amyloid beta: structure, biology and structure-based therapeutic development.Acta pharmacologica Sinica · 2017Review
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
Abstract
Alzheimer's disease (AD) is a common, chronic neurodegenerative disease that is thought to be caused by the neurotoxic effect of the Amyloid beta peptides (Abeta). We have hypothesized that the intrinsic Abeta calcium channel activity of the oligomeric Abeta polymer may be responsible for the neurotoxic properties of Abeta, and that Abeta channel blockers may be candidate AD therapeutics. As a consequence of a rational search paradigm based on the model structure of the Abeta channel, we have identified two compounds of interest: MRS2481 and an enatiomeric species, MRS2485. These are amphiphilic pyridinium salts that both potently block the Abeta channel and protect neurons from Abeta toxicity. Both block the Abeta channel with similar potency (approximately 500 nM) and efficacy (100%). However, we find that inhibition by MRS2481 is easily reversible, whereas inhibition by MRS2485 is virtually irreversible. We suggest that both species deserve consideration as candidates for Alzheimer's disease drug discovery.
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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.