Crosstalk between 2 organelles: Lysosomal storage of heparan sulfate causes mitochondrial defects and neuronal death in mucopolysaccharidosis III type C
Bibliographic record
Abstract
More than 30% of all lysosomal diseases are mucopolysaccharidoses, disorders affecting the enzymes needed for the stepwise degradation of glycosaminoglycans (mucopolysaccharides). Mucopolysaccharidosis type IIIC (MPS IIIC) is a severe neurologic disease caused by genetic deficiency of heparan sulfate acetyl-CoA: α-glucosaminide N-acetyltransferase (HGSNAT). Through our studies, we have cloned the gene, identified molecular defects in MPS IIIC patients and most recently completed phenotypic characterization of the first animal model of the disease, a mouse with a germline inactivation of the Hgsnat gene.(1) The obtained data have led us to propose that Hgsnat deficiency and lysosomal accumulation of heparan sulfate in microglial cells followed by their activation and cytokine release result in mitochondrial dysfunction in the neurons causing their death which explains why MPS IIIC manifests primarily as a neurodegenerative disease. The goal of this addendum is to summarize data yielding new insights into the mechanism of MPS IIIC and promising novel therapeutic solutions for this and similar disorders.
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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 | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.001 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.002 | 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".