ArticleScientific reports2020
Cellular polyamines condense hyperphosphorylated Tau, triggering Alzheimer's disease.
Article in Scientific reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 25 citations in OpenAlex.
- In Silico Isomerization Produces Apt Negative Data for VHTS Validation.Journal of chemical information and modeling · 2026Article
- Sequential co-extraction of gut microbial DNA and fecal polyamines enables integrated microbiome-metabolite profiling in an Alzheimer's disease mouse model.Scientific reports · 2026Article
- An efficient computational chemistry approach to generating negative data for drug discovery pipeline validation.Frontiers in bioinformatics · 2026Article
- Acetylcholinesterase as a Multifunctional Target in Amyloid-Driven Neurodegeneration: From Dual-Site Inhibitors to Anti-Agregation Strategies.International journal of molecular sciences · 2025Review
- Polyamination with spermidine enhances pathogenic tau conformations while reducing filamentous aggregate formation in vitro.The Biochemical journal · 2025Article
- A Single-Cell Metabolic Profiling Characterizes Human Aging via SlipChip-SERS.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2024Article
- Integrated spatial metabolomics and network pharmacology to explore the pharmacodynamic substances and mechanism of Radix ginseng-Schisandra chinensis Herb Couple on Alzheimer's disease.Analytical and bioanalytical chemistry · 2024Article
- Polyamine Dysregulation and Nucleolar Disruption in Alzheimer's Disease.Journal of Alzheimer's disease : JAD · 2024Article
- Calculated hydration free energies become less accurate with increases in molecular weight.PloS one · 2024Article
- Dysregulation ofCurrent Alzheimer research · 2024Article
- The Molecular Role of Polyamines in Age-Related Diseases: An Update.International journal of molecular sciences · 2023Review
- Review
- The Involvement of Polyamines Catabolism in the Crosstalk between Neurons and Astrocytes in Neurodegeneration.Biomedicines · 2022Review
- Tau liquid-liquid phase separation in neurodegenerative diseases.Trends in cell biology · 2022Review
- Virtual Screening and Hit Selection of Natural Compounds as Acetylcholinesterase Inhibitors.Molecules (Basel, Switzerland) · 2022Article
- Targeted Metabolomic Analysis in Alzheimer's Disease Plasma and Brain Tissue in Non-Hispanic Whites.Journal of Alzheimer's disease : JAD · 2022Article
- Phospho-Tau and Chromatin Landscapes in Early and Late Alzheimer's Disease.International journal of molecular sciences · 2021Review
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Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Many gaps in our understanding of Alzheimer's disease remain despite intense research efforts. One such prominent gap is the mechanism of Tau condensation and fibrillization. One viewpoint is that positively charged Tau is condensed by cytosolic polyanions. However, this hypothesis is likely based on an overestimation of the abundance and stability of cytosolic polyanions and an underestimation of crucial intracellular constituents - the cationic polyamines. Here, we propose an alternative mechanism grounded in cellular biology. We describe extensive molecular dynamics simulations and analysis on physiologically relevant model systems, which suggest that it is not positively charged, unmodified Tau that is condensed by cytosolic polyanions but negatively charged, hyperphosphorylated Tau that is condensed by cytosolic polycations. Our work has broad implications for anti-Alzheimer's research and drug development and the broader field of tauopathies in general, potentially paving the way to future etiologic therapies.
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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.