A bibenzyl compound 20C protects rats against 6-OHDA-induced damage by regulating adaptive immunity associated molecules

Parkinson's disease (PD) is a neurodegenerative disease with complicated pathogenesis. A novel bibenzyl compound 2-[4-hydroxy-3-(4-hydroxyphenyl)benzyl]-4-(4-hydroxyphenyl)phenol (20C) has been shown to have some neuroprotective effects, and its mechanism still needs further research. In this study, we used a 6-hydroxydopamine (6-OHDA)-induced PD rat model to evaluate the protective effect of 20C. Our study found that 20C could improve behavioral defects in 6-OHDA-lesion rats, decrease neuroinflammation and protect their DA neurons. It could inhibit the activity of inducible nitric oxide synthase (iNOS) induced by 6-OHDA, and lead to a decrease in the expression of nitrated-alpha-synuclein. When exposed to AMT-an inhibitor of iNOS, the nitrated alpha-synuclein in PC12 decreased, and 20C demonstrated the same function on nitrated-alpha-synuclein as AMT. Besides, we also found that nitrated-alpha-synuclein was displayed in microglia. And 20C could decrease the expression of antigen-presenting molecule major histocompatibility complex I (MHC I) in dopamine (DA) neurons and MHC II in microglia induced by 6-OHDA. So, these imply that nitrated-alpha-synuclein might act as an endogenous antigen activating adaptive immunity, and the neuroprotection of 20C might be associated with inhibiting the activity of iNOS, decreasing the expression of the antigen molecule nitrated-alpha-synuclein and the antigen presenting molecule MHC. Our results indicated that inhibiting iNOS might be an effective strategy to protect neurons from oxidative stress.

Automated summary

The novel compound 20C shows neuroprotective effects in a rat model of PD, improving behavioral deficits, reducing neuroinflammation, and protecting DA neurons. Its mechanism involves inhibiting iNOS activity, decreasing nitrated-alpha-synuclein expression, and reducing MHC molecule expression.