Structural disorder and the loss of RNA homeostasis in aging and neurodegenerative disease
Bibliographic record
Abstract
Whereas many cases of neurodegenerative disease feature the abnormal accumulation of protein, an abundance of recent literature highlights loss of RNA homeostasis as a ubiquitous and central feature of pathological states. In some diseases expanded repeats have been identified in non-coding regions of disease-associated transcripts, calling into question the relevance of protein in the disease mechanism. We review the literature in support of a hypothesis that intrinsically disordered proteins (proteins that lack a stable three dimensional conformation) are particularly sensitive to an age-related decline in maintenance of protein homeostasis. The potential consequences for structurally disordered RNA-binding proteins are explored, including their aggregation into complexes that could be transmitted through a prion-like mechanism. We propose that the spread of ribonucleoprotein complexes through the nervous system could propagate a neuronal error catastrophe at the level of RNA metabolism.
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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".