Pathogenic Feed-Forward Mechanisms in Alzheimer’s and Parkinson’s Disease Converge on GSK-3
Bibliographic record
Abstract
Alzheimer's disease (AD) and Parkinson's disease (PD) share many commonalities ranging from signaling deficits such as altered cholinergic activity, neurotrophin and insulin signaling to cell stress cascades that result in proteinopathy, mitochondrial dysfunction and neuronal cell death. These pathological processes are not unidirectional, but are intertwined, resulting in a series of feed-forward loops that worsen symptoms and advance disease progression. At the center of these loops is glycogen synthase kinase-3 (GSK-3), a keystone protein involved in many of the multidirectional biological processes that contribute to AD and PD neuropathology. Here, a unified overview of the involvement of GSK-3 in the major processes involved in these diseases will be presented. The mechanisms by which these processes are linked will be discussed and the feed-forward pathways identified. In this regard, this review will put forth the notion that combination therapy, targeting these multiple facets of AD or PD neuropathology is a necessary next step in the search for effective therapies.
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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) | 0.001 | 0.000 |
| Meta-epidemiology (broad) | 0.001 | 0.000 |
| Bibliometrics | 0.002 | 0.001 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.001 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".