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by reasonattlm
2354 days ago
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A prediction: the generic, low-cost drug dasatinib, a senolytic that selectively destroys senescent cells and can pass the blood-brain barrier, will be the best Alzheimer's treatment of the next decade, starting just as soon as the Mayo Clinic gets around to running a trial for that rather than focusing on fibrotic disease. https://doi.org/10.1111/acel.12840 "Tau transgenic mice with late stage pathology were treated with senolytics to remove senescent cells. Despite the advanced age and disease progression, MRI brain imaging and histopathological analyses indicated a reduction in total NFT density, neuron loss, and ventricular enlargement. Collectively, these findings indicate a strong association between the presence of NFTs and cellular senescence in the brain, which contributes to neurodegeneration." https://doi.org/10.1038/s41586-018-0543-y "Here we show a causal link between the accumulation of senescent cells and cognition-associated neuronal loss. We found that the a mouse model of tau-dependent neurodegenerative disease accumulates p16INK4A-positive senescent astrocytes and microglia. Clearance of these cells as they arise using INK-ATTAC transgenic mice prevents gliosis, hyperphosphorylation of both soluble and insoluble tau leading to neurofibrillary tangle deposition, and degeneration of cortical and hippocampal neurons, thus preserving cognitive function. Pharmacological intervention with a first-generation senolytic modulates tau aggregation." |
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