ArticleScientific reports2020
Hyperphosphorylated tau aggregation and cytotoxicity modulators screen identified prescription drugs linked to Alzheimer's disease and cognitive functions.
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 35 papers, 1 of them a synthesis that pooled it.
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Who cites it
35 citing papers in PubMed, 1 synthesis or guideline pooled it, 53 citations in OpenAlex.
- Is there a link between the use of benzodiazepines and related drugs and dementia? A systematic review of reviews.European geriatric medicine · 2022Pooled it
- Three-dimensional interactive network: Mitochondrial-metabolic-calcium homeostasis driving Alzheimer's disease.Genes & diseases · 2026Review
- Low-Dimensional Nanomaterials in Alzheimer's Disease: Current Applications.Current Alzheimer research · 2026Review
- Synergistic Neuroprotection in Tauopathic Mice via Green-Synthesized Silver Nanoparticles Co-delivering Methylene Blue and Moringa oleifera.Molecular neurobiology · 2025Article
- New Approach for Targeting Small-Molecule Candidates for Intrinsically Disordered Proteins.Methods and protocols · 2025Article
- Protein aggregation and neurodegenerative disease: Structural outlook for the novel therapeutics.Proteins · 2025Review
- Sensing Protein Structural Transitions with Microfluidic Modulation Infrared Spectroscopy.Biosensors · 2025Article
- Hyperphosphorylated tau-based Alzheimer's Disease drug discovery: Identification of inhibitors of tau aggregation and cytotoxicity.SLAS discovery : advancing life sciences R & D · 2025Article
- Advances in the structures, mechanisms and targeting of molecular chaperones.Signal transduction and targeted therapy · 2025Review
- Inspecting the Triazole Scaffold as Powerful Antifibril Agents against 2N4R Tau and α-Synuclein Aggregates.ACS omega · 2025Article
- RhoA/ROCK/GSK3β Signaling: A Keystone in Understanding Alzheimer's Disease.Current issues in molecular biology · 2025Review
- Effects of Heparan Sulfate Trisaccharide Containing Oleanolic Acid in Attenuating Hyperphosphorylated Tau-Induced Cell Dysfunction Associated with Alzheimer's Disease.Journal of medicinal chemistry · 2025Article
- Natural products against tau hyperphosphorylation-induced aggregates: Potential therapies for Alzheimer's disease.Archiv der Pharmazie · 2025Review
- Alzheimer's Disease: Exploring the Landscape of Cognitive Decline.ACS chemical neuroscience · 2024Review
- Pilot Study for Deciphering Post-Translational Modifications and Proteoforms of Tau Protein by Capillary Electrophoresis-Mass Spectrometry.Journal of proteome research · 2024Article
- Article
- Oligomeric Tau-induced oxidative damage and functional alterations in cerebral endothelial cells: Role of RhoA/ROCK signaling pathway.Free radical biology & medicine · 2024Article
- Physiological and pathological effects of phase separation in the central nervous system.Journal of molecular medicine (Berlin, Germany) · 2024Review
- Hyperphosphorylated Tau Inflicts Intracellular Stress Responses that Are Mitigated by Apomorphine.Molecular neurobiology · 2024Article
- Selection of lansoprazole from an FDA-approved drug library to inhibit the Alzheimer's disease seed-dependent formation of tau aggregates.Frontiers in aging neuroscience · 2024Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
The neurodegenerative Alzheimer's disease (AD) affects more than 30 million people worldwide. There is thus far no cure or prevention for AD. Aggregation of hyperphosphorylated tau in the brain correlates with the cognitive decline of patients of AD and other neurodegenerative tauopathies. Intracerebral injection of tau aggregates isolated from tauopathy brains causes similar pathology in the recipient mice, demonstrating the pathogenic role of abnormally phosphorylated tau. Compounds controlling the aggregation of hyperphosphorylated tau therefore are probable modulators for the disease. Here we report the use of recombinant hyperphosphorylated tau (p-tau) to identify potential tauopathy therapeutics and risk factors. Hyperphosphorylation renders tau prone to aggregate and to impair cell viability. Taking advantage of these two characters of p-tau, we performed a screen of a 1280-compound library, and tested a selective group of prescription drugs in p-tau aggregation and cytotoxicity assays. R-(-)-apomorphine and raloxifene were found to be p-tau aggregation inhibitors that protected p-tau-treated cells. In contrast, a subset of benzodiazepines exacerbated p-tau cytotoxicity apparently via enhancing p-tau aggregation. R-(-)apomorphine and raloxifene have been shown to improve cognition in animals or in humans, whereas benzodiazepines were linked to increased risks of dementia. Our results demonstrate the feasibility and potential of using hyperphosphorylated tau-based assays for AD drug discovery and risk factor identification.
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