Cellulose ethers reduce amyloid‐beta pathology in <i>in vitro</i> and <i>in vivo</i> Alzheimer’s disease model
Bibliographic record
Abstract
Abstract Background Alzheimer’s disease (AD) is a progressive neurodegenerative disease and the most prevalent cause of dementia. Neuropathologically, AD is characterized by amyloid‐beta (Aβ) aggregation. This is thought to be a primary pathological event impairing cellular homeostasis, neurotransmitters, inflammatory response, induces misfolding of other proteins and consequently leads to synaptic/neuronal loss. To date, no therapeutics are available to cure AD. Hence, we aimed to determine the therapeutic effects of cellulose ether (CE)‐based compounds for the treatment of AD. Method We tested different concentrations of the CE TC‐5RW in vitro for its effect on Aβ aggregation by Thioflavin T assay. Similarly, we performed MTT assays to determine cell viability of human neuroblastoma (SH‐SY5Y) cells treated with Aβ aggregates formed in the presence or absence of TC‐5RW. In vivo, transgenic 5xFAD (expressing human APP and PSEN1 transgenes harboring in total 5 mutations associated with familial AD) mice were treated at the age of 6 weeks with a single subcutaneous injection of TC‐5RW at a dosage of 4g/kg. Following this treatment, the mice were euthanized at the age of 10 months and brains were harvested for further biochemical (Western blotting) and immunohistochemical analyses. Result Our in vitro Thioflavin T assay results indicated that TC‐5RW had beneficial effects and at 0.25 % and 1 % TC‐5RW concentrations inhibited Aβ aggregation and accumulation. The MTT results showed that TC‐5RW increased cell viability of Aβ exposed SH‐SY5Y cells. Likewise, in vivo, the treatment with TC‐5RW significantly reduced the amount of oligomeric and monomeric forms of Aβ in the brains of 5xFAD+TC‐5RW mice compared to control 5xFAD mice. We performed Aβ6E10 immunofluorescence staining to analyse the number of Aβ plaques, and Aβ immunoreactivity in the hippocampus and cortex of the mice. The treatment with TC‐5RW significantly alleviated the number of Aβ plaques and immunofluorescence reactivity in the hippocampus and cortex of 5xFAD+TC‐5RW mice compared to control 5xFAD mice. These in vitro and in vivo results indicate that TC‐5RW reduces Aβ pathology. Conclusion Taken together, our results and the safety profile (FDA approved) of CEs, suggest that these compounds have promising potential for the development of therapeutics against AD.
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How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".