TNF alpha unmasks enteric malate aspartate shuttle dysfunction bridging Parkinson disease and intestinal inflammation - PubMed
5 hours ago
- #Parkinson's disease
- #enteric nervous system
- #TNF alpha
- Gastrointestinal dysfunction often precedes motor symptoms in Parkinson's disease, suggesting early involvement of the enteric nervous system.
- TNF alpha enhances alpha-synuclein accumulation and impairs the malate-aspartate shuttle, a key mitochondrial energy pathway, in induced pluripotent stem cell-derived enteric neurons and glia.
- This metabolic dysfunction shifts cells toward glutamine oxidation and reduces mitochondrial function, partially rescued by the compound Chicago-Sky-Blue 6B.
- Inflammation-associated metabolic suppression and alpha-synuclein upregulation are found in human gut tissue from inflammatory bowel disease patients, indicating general hallmarks of intestinal inflammation beyond Parkinson's disease.
- The study establishes patient-derived enteric lineages as a platform to model inflammatory enteric nervous system pathology.