Degradation of CNTNAP2 is mediated by both macroautophagy‐lysosome pathway and ubiquitin‐proteasome pathway
Bibliographic record
Abstract
Abstract Background Recent studies suggested Contactin‐associated protein‐like 2 (CNTNAP2) as a novel risk gene for Alzheimer’s disease (AD). Reduced expression levels of CNTNAP2 were found in the brains of AD patients. However, the mechanisms underlying CNTNAP2 protein degradation remain elusive. Method HEK and N2a cells transfected with human CNTNAP2 plasmid were treated with cycloheximide, lysosome inhibitors, and proteasome inhibitors. Immunoprecipitation was performed to study the interaction between CNTNAP2 and ubiquitin. Immunofluorescent staining was performed to investigate colocalization. Result Human CNTNAP2 protein has a half‐life of approximately 4 hours. CNTNAP2 protein has a glycosylated mature form on the cell membrane and an intracellular immature form. Mature CNTNAP2 was increased by lysosome inhibitors in a dose‐ and time‐dependent manner, while immature CNTNAP2 was increased by proteasome inhibitors dose‐ and time‐dependently. In addition, CNTNAP2 was co‐immunoprecipitated with ubiquitin and was increased by macroautophagy inhibitor 3‐MA. Immunofluorescent staining further showed the co‐localization of CNTNAP2 with ubiquitin and lysosome marker LAMP1. Conclusion Human CNTNAP2 is degraded via both lysosome and proteasome pathways. Dysregulation of lysosome and ubiquitin‐proteasome pathways have been implicated in AD. Therefore, the present degradation study of a risk gene may deepen the current understanding of AD pathogenesis.
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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) | 0.001 | 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".