Bibliographic record
Abstract
Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) is a rare, progressive, and debilitating neurodegenerative disease. ARSACS is caused by mutations in the SACS molecular chaperone gene, which encodes Sacsin, a large, 520 kDa multidomain protein called. This protein is highly expressed in the central nervous system, including Purkinje cells, the only neurons that provide output from the cerebellar cortex. While the explicit function of Sacsin is not well understood, mitochondrial dynamics have been suggested based on reports of impaired mitochondrial function in Sacsin knockdown cell models. Using a neuronal-like cell line and patient-derived fibroblasts, we aimed to elucidate the role of Sacsin and investigate its relationship to mitochondrial dynamics. To date, we have established submitochondrial localization of Sacsin to the outer mitochondrial membrane along with reduced expression of both transcript and protein levels in patient-derived fibroblasts. Immunofluorescence staining revealed that a reduction in Sacsin protein compromises multiple parameters of mitochondrial health, such as mitochondrial membrane potential, intracellular calcium levels, respirasome activity, and trafficking. In addition, given the high demand for energy in neurons, a reduction in mitochondrial function and localization leads to inefficient energy distribution. Consequently, there is a neuronal dysfunction consistent with abnormal morphology, calcium signalling and a reduction in cell viability observed in patient neurons derived from induced pluripotent stem cells. Therefore, these findings suggest that downregulation of the Sacsin protein results in impaired mitochondrial function and trafficking that causes neuronal dysfunction and contributes to neuronal cell death. Keywords: ARSACS; Sacsin; Neurodegeneration; Mitochondria; Protein.
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 | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.001 | 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 | 0.000 |
| Research integrity | 0.001 | 0.001 |
| Insufficient payload (model declined to judge) | 0.002 | 0.001 |
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".