Role of TLR7/8 in the pathogenesis of Parkinson’s disease meant as Autoimmunity disorders

Michela Campolo, Irene Paterni

Abstract

Neuroinflammation and autoimmune mechanisms have been recognized to have a key part in the pathogenesis of Parkinson’s disease (PD). Therefore, we evaluated the role of Toll-like receptors (TLRs) as a link between inflammation and autoimmunity in PD. We performed an in vivo model of PD, by 1-metil 4-fenil 1,2,3,6-tetraidro-piridina (MPTP) administration for 7 days, in single KO mice for TLR7, TLR 8 and TLR9; and in double KO mice for TLR 7/8-/-. All animals were compared with WT animals used as a control group. The result obtained demonstrated that the genetic absence of TLR 7 and 8 modified PD pathway increasing the immunoreactivity for TH and DAT compared to PD groups and decreasing microglia and astrocytes activation. Moreover, the deletion of TLR7 and TLR8 significantly reduced T-cell production in the substantia nigra and lymph nodes, suggesting a reduction of T cell activation. Therefore, our result highlights a possibility that an immunotherapy approach by using a dual antagonist of TLR 7 and 8, could be considered as a possible target to develop new therapies for Parkinson diseases.