TDP‐43 aggregation and inhibition using antibodies targeting RRM2‐CTD domain
Bibliographic record
Abstract
Abstract Background TDP‐43 is a highly conserved protein localized to the nucleus. Under pathological conditions, it forms fibrillar aggregates, characteristic of Amyotrophic Lateral Sclerosis (ALS) progression. The exact mechanism of TDP‐43 aggregation and formation into a pathological state has yet to be elucidated, but is an important therapeutic target to consider. Methods In vitro full‐length phosphorylated TDP‐43 (pS410)protein was agitated and aged, with and without the presence of TDP‐43 specific antibodies. Immunoblotting was used to confirm the binding of antibodies to TDP‐43. Aggregation was monitored using spectroscopic methods, Thioflavin T (ThT), and turbidity. Transmission electron microscopy (TEM) visualized the formation and structure of phospho‐TDP‐43 aggregates. Results The agitation and extensive aging (days) were required to induce aggregation of insoluble phospho‐TDP‐43 aggregates and formation of ThT positive fibrils. When exposed to an antibody specific to the RRM2‐CTD domain on TDP‐43, aggregation was inhibited in a concentration‐dependent manner and fibril formation was reduced. Conclusions Inhibition of TDP‐43 aggregation and fibril formation using antibodies demonstrates the potential for epitope‐specific treatment of TDP‐43 proteinopathies. 1) Esposto, J., & Martic‐Milne, S. (2021). Phosphorylated TAR DNA‐binding protein‐43: aggregation and antibody‐based inhibition. Biochimica et Biophysica Acta (BBA) ‐ Molecular Basis of Disease, 1867, https://doi.org/10.1016/j.bbadis.2021.166234.
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
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 | 0.001 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.001 |
| 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".