Overview
- In the Nature study, researchers introduced tiny amounts of patient-derived misfolded alpha‑synuclein into the small intestines of mice and tracked its movement into the brain.
- Muscularis macrophages, rather than enteric neurons, contained most of the aggregated protein and displayed endolysosomal dysfunction consistent with impaired clearance.
- After engulfing alpha‑synuclein, the gut macrophages signaled to expand ‘gut‑instructed’ T cells that then migrated from the enteric nervous system to the brain.
- Macrophage depletion in the gut or T‑cell blockade lowered central alpha‑synuclein pathology, mitigated neurodegeneration and improved motor performance in the models.
- Led by the UK Dementia Research Institute at UCL, the preclinical work points to immune‑targeting strategies and blood inflammatory markers as next steps, with clinical relevance yet to be established.