Mechanistic description
Specific gut bacterial strains produce short-chain fatty acids (SCFAs) that cross the blood-brain barrier and directly modulate α-synuclein aggregation through epigenetic modifications of chaperone proteins. Therapeutic supplementation with SCFA-producing bacteria could prevent or reverse pathological protein aggregation in PD.
Evidence for (5)
Targeting autophagy using small-molecule compounds to improve potential therapy of Parkinson's disease.
Recombinant pro-CTSD (cathepsin D) enhances SNCA/α-Synuclein degradation in α-Synucleinopathy models.
A ROS-Responsive nanoparticle for nuclear gene delivery and autophagy restoration in Parkinson's disease therapy.
Preclinical Alzheimer's disease shows alterations in circulating neuronal-derived extracellular vesicle microRNAs in a multiethnic cohort.
The Crosstalk Between Sepsis-Associated Encephalopathy and Alzheimer's Disease: Identifying Potential Biomarkers and Therapeutic Targets for Cognition.
Evidence against (2)
Short-chain fatty acids produced by gut microbiota promoted microglial activation and motor deficits in an alpha-synuclein Parkinson model, contradicting a uniformly protective SCFA/disaggregation model.
Reviews of SCFAs, alpha-synuclein, neuroinflammation, and redox stress describe bidirectional and context-dependent effects rather than direct disaggregation evidence.