Parkinson’s disease related proteins PINK1 and Parkin are major regulators of the immune system
Bibliographic record
Abstract
Abstract Parkinson’s disease (PD) is a neurodegenerative disorder linked to the loss of dopaminergic neurons (DN) in the substantia nigra. Although the mechanisms triggering the loss of DN are unclear, mitochondrial dysfunction and inflammation are viewed as playing a key role. PINK1 and Parkin are major regulators of mitophagy and failure in this pathway in DNs is hypothesized to enhanced oxidative stress and cause cell death. However, we showed that PINK1 and Parkin play also a role in adaptive immunity by repressing mitochondrial antigen presentation (MitAP) (Matheoud et al., Cell 2016), suggesting that autoimmune mechanisms participate in the aetiology of PD. Here, following on the finding that LPS triggers MitAP in vitro and in vivo, we present evidence that intestinal infection with Gram - bacteria in Pink1 KO mice increases the release of pro-inflammatory cytokines, activates MitAP and induces autoimmune mechanisms eliciting the activation of cytotoxic mitochondria-specific CD8+ T cells. Remarkably, infection in these mice also leads to the emergence of severe motor impairment, reversed by L-DOPA treatment, accompanied by a sharp decrease in the density of dopaminergic axonal varicosities in the striatum. These data support the role of PINK1 as a modulator of the immune system and provide a new pathophysiological model where intestinal infection acts as a triggering event in PD, highlighting the relevance of the gut-brain axis in the disease.
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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 | 0.001 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 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".