Downregulation of stearoyl‐CoA desaturase in Huntington's disease
Bibliographic record
Abstract
Huntington's disease (HD) is a neurodegenerative disorder characterized by motor, psychiatric and cognitive dysfunction. The disease is caused by the abnormal expansion of a polyglutamine stretch in the N‐terminal region of huntingtin, a ubiquitous protein with unknown function. Mutant huntingtin has been recently shown to interfere with the nuclear localization of the sterol‐regulatory element binding protein (SREBP)‐1, a transcription factor that is key to the expression of enzymes involved in the synthesis of fatty acids. THE OBJECTIVE of this work was to assess whether dysregulation of SREBP‐1 activity affects fatty acid metabolism in HD brains. Using real‐time PCR we have found that expression of stearoyl‐CoA desaturase (SCD), the main mammalian desaturase for the production of monounsaturated fatty acids and a major transcriptional target of SREBP‐1, is down‐regulated in cell and animal models of HD. SCD down‐regulation across HD brain regions mirrors the pattern of neurodegeneration in HD, with the striatum displaying the strongest reduction in SCD expression. Reduced expression of SCD in HD brains is likely to result in an altered ratio between saturated and unsaturated fatty acids, with subsequent perturbations in lipid and membrane composition and altered membrane fluidity, thus representing an important determinant of neural dysfunction in HD. This research is supported by the Huntington Society of Canada and the Canadian Institutes of Health Research.
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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".