Mechanisms of peripheral alpha-synuclein preformed fibril transcytosis across the blood-brain barrier

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Description

PMID:39652643 demonstrated that peripheral blood alpha-synuclein preformed fibrils (PFFs) cross the blood-brain barrier via endothelial Lag3 endocytosis and aggravate neurodegeneration in PD models. However, the molecular mechanism of transcytosis, whether endogenous peripheral alpha-synuclein PFFs contribute to sporadic PD, and which additional receptors beyond Lag3 mediate brain entry are unresolved questions.

Evidence summary

Resolved by hypothesis h-var-08a4d5c07a: Gut Microbiome Remodeling to Prevent Systemic NLRP3 Priming in Neurodegeneration. Score: 0.907. Supporting PMIDs: 33875891, 30610225, 31748742, 27519954, 33741860.

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