nNOSα and nNOSβ localization to aggresome‐like inclusions is dependent on HSP90 activity
Bibliographic record
Abstract
Nitric oxide (NO) is a highly reactive gas that participates in many physiological processes including neuroplasticity and neuronal survival. In brain neurons, NO is produced by two variants of neuronal nitric oxide synthase (nNOS), nNOSalpha and nNOSbeta. The activity of nNOSalpha is tightly regulated at the transcriptional and post-transcriptional levels. Heat shock protein 90 (HSP90) regulates nNOSalpha activity by facilitating heme insertion into the nNOSalpha monomer, resulting in increased NO production. HSP90 also regulates nNOSalpha degradation through the proteasome pathway. Here, we show in vitro that inhibition of HSP90 with geldanamycin increases nNOS mobility and induces formation of aggresome-like inclusions containing both nNOSalpha and nNOSbeta in primary cortical neurons. We also report the formation of endogenous nNOS-containing aggresome-like inclusions in healthy, untreated, mature primary cortical neurons. We propose that nNOS aggregation may be an additional mechanism for regulating nNOS activity, as has been proposed for inducible nitric oxide synthase. These findings reveal a new role for HSP90 in regulating nNOS sub-cellular localization and underscore the complexity of nNOS regulatory mechanisms.
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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".