Expression of Stathmin, a Developmentally Controlled Cytoskeleton-Regulating Molecule, in Demyelinating Disorders
Bibliographic record
Abstract
Understanding the biological relevance of reexpression of developmental molecules in pathological conditions is crucial for the development of new therapies. In this study, we report the increased expression of stathmin, a developmentally regulated tubulin-binding protein, in the brains of patients with multiple sclerosis (MS). In physiological conditions, stathmin immunoreactivity was observed in polysialic acid-neural cell adhesion molecule-positive migratory progenitors in the subventricular zone, and its expression progressively decreased as the cells matured into oligodendrocytes (OLs). In MS patients, however, stathmin levels were elevated in 2',3'-cyclic nucleotide 3'-phosphodiesterase-positive OLs, in 10 of 10 bioptic samples analyzed. Increased levels of stathmin were confirmed by Western blot analysis of normal-appearing white matter samples from MS brains. In addition, using mass spectrometry, stathmin was identified as the main component of a specific myelin protein fraction consistently increased in MS preparations compared with controls. To test the biological relevance of increased stathmin levels, primary OL progenitors were transfected using a myc-tagged stathmin cDNA and were allowed to differentiate. Consistent with a distinct role played by this molecule in cells of the OL lineage at different developmental stages, transient transfection in progenitors favored the bipolar migratory phenotype but did not affect survival. However, sustained stathmin levels in differentiating OLs, because of overexpression, resulted in enhanced apoptotic susceptibility. We conclude that stathmin expression in demyelinating disorders could have a dual role. On one hand, by favoring the migratory phenotype of progenitors, it may promote myelin repair. On the other hand, stathmin in mature OLs may indicate cell stress and possibly affect survival.
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How this classification was reachedexpand
Full frame distilled prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. Learned from the 10,348 direct Codex labels and 10,348 direct Gemma labels. Candidate is the union of thresholded teacher heads; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels or direct frontier model labels.
Codex and Gemma teacher scores by category
| 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 teacher head, 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".