Supplementary file 1_Cellular prion protein levels modulate nigrostriatal vulnerability to α-synuclein oligomers in Parkinson’s disease.docx

Immunohistochemical analysis at 30 days post-injection revealed that dopaminergic vulnerability was determined by PrP^C expression levels. Tg20 mice exhibited reduced tyrosine hydroxylase immunoreactivity in the caudate-putamen, while PrnpKO mice were protected. Behavioral assessment showed that PrP^C levels modulate baseline motor performance, with Tg20-αSynO mice consistently displaying the most severe motor impairment.

RT-qPCR analysis of striatal transcripts/mRNA levels revealed genotype-specific neuroinflammatory responses to αSynO. WT mice mounted a selective anti-inflammatory Arginase 1 response, PrnpKO mice partially resolved their basal pro-inflammatory profile, whereas Tg20 mice exhibited pro-inflammatory exacerbation with significant upregulation of Tnfα and Il1β. Together, these findings identify PrP^C expression levels as an important modulator of nigrostriatal vulnerability and neuroinflammatory phenotype in response to αSynO, supporting the hypothesis that PrP^C contributes to αSynO-mediated pathogenic mechanisms.</p>