Disruption of Plexin-A1 signaling by FTX-101: mode of action and effect on oligodendrocyte biology
Bibliographic record
Abstract
BACKGROUND AND PURPOSE: In the absence of effective remyelination therapies for neurodegenerative disorders, we have synthesized FTX-101, a therapeutic peptide rationally designed to enhance the recruitment and maturation of oligodendrocyte precursors. EXPERIMENTAL APPROACH: Given that Sema3A signaling through the NRP1/Plexin-A1 receptor complex inhibits remyelination, we employed FTX-101 to disrupt the assembly of this receptor complex at the transmembrane interface. We conducted in vitro analyses to assess the effects on the migration, differentiation, and myelination of oligodendrocytes. FTX-101 was evaluated in a murine oligodendroglial cell line as well as in oligodendrocytes derived from human fibroblasts. KEY RESULTS: FTX-101 functions as a membrane-targeting peptide with exceptional attributes. Notably, while of lipophilic nature it demonstrates water solubility, it is highly specific for the NRP1/Plexin-A1 receptor system and when lyophilized remains stable for an extended amount of time. Our findings indicated that FTX-101 effectively disrupts the NRP1/Plexin-A1 receptor complex and mitigated the inhibitory influence of Sema3A on oligodendrocyte migration and differentiation, thereby facilitating increased myelin sheathing around axons. CONCLUSION AND IMPLICATIONS: FTX-101 enhanced the recruitment of oligodendrocytes and promoted myelination, addressing critical medical needs in demyelinating conditions. Specificity, solubility in water, and enduring stability render FTX-101 a highly promising candidate for a first-in-class therapeutic agent.
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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 | 0.001 | 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".