Deficiency of the serine peptidase Kallikrein 6 does not affect the levels and the pathological accumulation of a‐synuclein in mouse brain
Bibliographic record
Abstract
Abstract Several lines of evidence indicate that the propagation of misfolded α‐synuclein (α‐syn) plays a central role in the progression and manifestation of Parkinson's disease. Pathogenic α‐syn species can be present in the extracellular space. Thus, the identification and modulation of the key enzymes implicated in extracellular α‐syn turnover becomes vital. Kallikrein peptidase 6 has been identified as one of the major α‐syn degrading enzymes and has been implicated in the clearance of extracellular α‐syn. However, the physiological role of this enzyme in regulating α‐syn, in vivo, still remains elusive. Here, by utilizing Klk6 knock‐out (Klk6−/−) mice as our experimental model, we provide insight into the physiologic relevance of endogenous KLK6 expression on α‐syn processing. Behavioral phenotyping showed that Klk6−/− mice display no gross behavioral abnormalities. Further in vivo characterization of this mouse model, in the context of α‐syn accumulation, showed that KLK6 deletion had no impact on the protein levels of intracellular or extracellular α‐syn. Upon in vivo administration of α‐syn pre‐formed fibrils (PFF), α‐syn pathologic accumulations were evident both in the brains of Klk6−/−mice and wt mice without significant differences. Intrastriatal delivery of active KLK6, did not affect secreted α‐syn levels observed in the A53T α‐syn over‐expressing mice. These findings suggest that in the in vivo setting of PFF pathology induction, KLK6 alone is not able to modulate pathology transmission. Our study raises implications for the use of recombinant α‐syn fibrils in α‐syn turnover studies. image
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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) | 0.001 | 0.001 |
| Meta-epidemiology (broad) | 0.001 | 0.001 |
| Bibliometrics | 0.001 | 0.000 |
| Science and technology studies | 0.000 | 0.001 |
| Scholarly communication | 0.001 | 0.001 |
| Open science | 0.001 | 0.000 |
| Research integrity | 0.001 | 0.002 |
| Insufficient payload (model declined to judge) | 0.003 | 0.002 |
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".