Related Experiment Video
Updated: Jan 30, 2026
09:18
A Gut-on-a-Chip Model to Study the Gut Microbiome-Nervous System Axis
Published on: July 28, 2023
3.5K
Intestinal macrophages modulate synucleinopathy along the gut-brain axis
Sebastiaan De Schepper1,2, Viktoras Konstantellos3, James A Conway3
1UK Dementia Research Institute, University College London, London, UK. sebastiaan.deschepper@uantwerpen.be.
Nature
|January 28, 2026
Summary
Muscularis macrophages initiate Parkinson's disease (PD) pathology in the gut's nervous system. Targeting these cells reduces pathology spread, neurodegeneration, and motor deficits, offering potential early PD biomarkers.
Area of Science:
- Neuroscience
- Immunology
- Gastroenterology
Background:
- Parkinson's disease (PD) may originate in the enteric nervous system (ENS), with alpha-synuclein (αS) pathology spreading to the brain.
- Constipation and T cell responses to αS in PD patients suggest early peripheral immune involvement.
Purpose of the Study:
- Investigate the cellular mechanisms triggering αS pathology in the ENS and its gut-brain axis spread.
- Determine the role of muscularis macrophages (ME-Macs) in PD pathogenesis.
Main Methods:
- Utilized PD models to study ME-Macs' role in αS pathology and neurodegeneration.
- Examined αS presence, endolysosomal dysfunction, and T cell modulation in ME-Macs.
- Assessed the impact of directed ME-Mac depletion on PD pathology and motor function.
Main Results:
- ME-Macs were found to contain misfolded αS and exhibit endolysosomal dysfunction.
- ME-Macs modulate T cell expansion, which travels from the ENS to the brain.
- ME-Mac depletion reduced αS pathology, T cell expansion, neurodegeneration, and motor dysfunction.
Conclusions:
- ME-Macs act as early cellular initiators of αS pathology along the gut-brain axis in PD.
- These findings suggest ME-Macs are crucial in PD pathogenesis and could be targets for early biomarkers.
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