Resumption of Autophagy by Ubisol-Q<sub>10</sub> in Presenilin-1 Mutated Fibroblasts and Transgenic AD Mice: Implications for Inhibition of Senescence and Neuroprotection
Bibliographic record
Abstract
Alzheimer’s disease (AD) is the most prevalent form of dementia and is associated with loss of memory, amyloid-beta plaque buildup, and neurofibrillary tangles. These features might be a result of neuronal cell death in the cerebral cortex and hippocampal regions of the brain. AD pathologies can be attributed to a variety of biochemical consequences including mitochondrial dysfunction, increased oxidative stress, and autophagy inhibition. Unfortunately, current therapeutics are limited only to symptomatic relief and do not halt the progression of neurodegeneration. Previous in vitro experiments have shown that a water-soluble formulation of coenzyme-Q 10 , Ubisol-Q 10 , can stabilize the mitochondria, prevent oxidative stress, and inhibit premature senescence in fibroblasts of AD patients. Since autophagy plays a critical role in maintenance and survival of neurons, we hypothesized that Ubisol-Q 10 treatment could result in resumption of autophagy. Indeed, we observed induction of autophagy by Ubisol-Q 10 treatment in AD fibroblasts as well as in the brains of transgenic AD mice. We found increased expression of autophagy-related genes beclin-1 and JNK1 following Ubisol-Q 10 treatment of AD fibroblasts. These results were confirmed at the protein level by immunofluorescence and Western blotting. Interestingly, despite reduction of oxidative stress in cells due to Ubisol-Q 10 treatment, autophagy inhibition leads to resumption of premature senescence in these PS-1 mutated fibroblasts indicating that autophagy is critical to prevent the senescence phenotype. Withdrawal of Ubisol-Q 10 treatment also leads to the return of the senescence phenotype in AD fibroblasts indicating that constant supplementation of Ubisol-Q 10 is required. Additionally, Ubisol-Q 10 supplementation in the drinking water of double transgenic AD mice leads to increased expression of beclin-1 and JNK1 in the cortical region. Thus, the activation of autophagy by Ubisol-Q 10 could be the mechanism for its ability to halt the progression of AD pathology in transgenic AD mice shown previously.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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) | 0.000 | 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 teacher head, 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".