Significance of cytosolic cathepsin D in Alzheimer's disease pathology: Protective cellular effects of PLGA nanoparticles against β‐amyloid‐toxicity
Why this work is in the frame
A frame that forgets how it found something cannot be audited. These are the routes that admitted this work.
Bibliographic record
Abstract
BACKGROUND: Evidence suggests that amyloid β (Aβ) peptides play an important role in the degeneration of neurons during the development of Alzheimer's disease (AD), the prevalent cause of dementia affecting the elderly. The endosomal-lysosomal system, which acts as a major site for Aβ metabolism, has been shown to exhibit abnormalities in vulnerable neurons of the AD brain, reflected by enhanced levels/expression of lysosomal enzymes including cathepsin D (CatD). At present, the implication of CatD in selective neuronal vulnerability in AD pathology remains unclear. METHODS: We evaluated the role of CatD in the degeneration of neurons in Aβ-treated cultures, transgenic AD mouse model (that is 5xFAD) and post mortem AD brain samples. RESULTS: -induced toxicity in cortical cultured neurons is associated with impaired lysosomal integrity, enhanced levels of carbonylated proteins and tau phosphorylation. The cellular and cytosolic levels/activity of CatD are also elevated in cultured neurons following exposure to Aβ peptide. Additionally, we observed that CatD cellular and subcellular levels/activity are increased in the affected cortex, but not in the unaffected cerebellum, of 5xFAD mice and post mortem AD brains. Interestingly, treatment of cultured neurons with nanoparticles PLGA, which targets lysosomal system, attenuated Aβ toxicity by reducing the levels of carbonylated proteins, tau phosphorylation and the level/distribution/activity of CatD. CONCLUSION: Our study reveals that increased cytosolic level/activity of CatD play an important role in determining neuronal vulnerability in AD. Additionally, native PLGA can protect neurons against Aβ toxicity by restoring lysosomal membrane integrity, thus signifying its implication in attenuating AD.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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) | 0.001 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| 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 it