Several studies have reported that PrP synthetic peptides induce microglial activation. The identification of cell surface molecules that mediate the PrP synthetic peptides interaction with microglia is of great importance as it represents the first point of intervention in the events leading to the pathophysiology of prion diseases. Our approach to investigate the role of CD36 in the PrP106–126-induced microglia activation derived from consideration of its well-documented role in other protein misfolding-diseases such as Alzheimer’s disease. We started by examining the effect of exposure to PrP106–126 on the expression of CD36 gene in BV2 cells. The mRNA level of CD36 increased significantly after 6 h of exposure to the prion peptides and steadily decreased during the time interval between 12 and 24 h. The general pattern of the expression of CD36 mRNA observed in this experiment is similar to that that we have reported in a recent study. In that study, the concentration of PrP106–126 was lower and the increase in CD36 started earlier but started to decrease at 6 h. Our result is consistent with many reports in the literature supporting the idea of inducible overexpression of CD36 in microglia after exposure to amyloid fibril,Benzoylaconine and is compatible with a possible participation of CD36 in PrP106–126induced microglial activation. Our approach then consisted of examining the effect of blocking CD36 by monoclonal antibody on several parameters of microglial activation. The adoption of this approach was motivated by the fact that CD36 tends to act as a component of a cell surface receptor complex that mediates the binding of microglia to fibrillar proteins or other ligands. We hypothesized that by blocking CD36 with its monoclonal antibody we could competitively inhibit the formation of the receptor complex and this would reveal its role in the process of microglial activation upon stimulation with prion peptides. Proinflammatory cytokines are Licochalcone-C important effector molecules that act as proinflammatory factors and are thought to paly an important role in neurodegeneration. There have been conflicting reports of the effect of prion peptides on the level of inflammatory cytokines in microglia. In this study, we showed that PrP106–126 induced a significant increase in the expression of IL1b, IL-6 and TNF-a both at mRNA and protein levels. Interestingly, pretreatment with anti-CD36 monoclonal antibody significantly abrogated the PrP106–126-induced increase in the mRNA expression of the three cytokines. At the protein level, however, the blocking effect of anti-CD36 antibody was maintained only for IL-6, IL-1b, albeit not significantly for the latter. In contrast, CD36 blockade did not alter PrP106–126-induced increase in the protein level of TNF-a although it significantly downregulated the increase in its mRNA transcription induced by PrP106–126 treatment. Finally, the LRRK2-overexpressing SH-SY5Y clone from which we prepared the cell lysate for immunoprecipitation was the neuronal cell line known to express a higher level of tau than cells of other tissue types. In the present study, we identified a Thr181 as one of the direct target sites of tau for LRRK2. It has been shown in mouse models that the level of tau phosphorylation at Ser202/Thr205 in the brain was elevated in R1441G and G2019S LRRK2 transgenic mice and diminished in LRRK2-knockout mice. However, we did not detect LRRK2 phosphorylation of tau at any Ser-residues or at Thr205, nor did we observe any increase in the phosphorylation level of tau Thr205 upon overexpression of LRRK2 in SH-SY5Y cells. In a Drosophila model, on the other hand, it has been reported that dopaminergic neurons of G2019S LRRK2-transgenic flies exhibited hyperphosphorylation of tau at Thr212, which was ascribed to kination by the activated GSK-3b homologue, and not to direct kination by LRRK2.