β-Arrestin1 regulates γ-secretase complex assembly and modulates amyloid-β pathology
Bibliographic record
Abstract
Alzheimer's disease (AD) is a progressive and complex neurodegenerative disease in which the γ-secretase-mediated amyloid-β (Aβ) pathology plays an important role. We found that a multifunctional protein, β-arrestin1, facilitated the formation of NCT/APH-1 (anterior pharynx-defective phenotype 1) precomplex and mature γ-secretase complex through its functional interaction with APH-1. Deficiency of β-arrestin1 or inhibition of binding of β-arrestin1 with APH-1 by small peptides reduced Aβ production without affecting Notch processing. Genetic ablation of β-arrestin1 diminished Aβ pathology and behavioral deficits in transgenic AD mice. Moreover, in brains of sporadic AD patients and transgenic AD mice, the expression of β-arrestin1 was upregulated and correlated well with neuropathological severity and senile Aβ plaques. Thus, our study identifies a regulatory mechanism underlying both γ-secretase assembly and AD pathogenesis, and indicates that specific reduction of Aβ pathology can be achieved by regulation of the γ-secretase assembly.
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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) | 0.000 | 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 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".