FIGURE 6.

[FAA:TA] NPs reduce microglial Iba-1 expression and NF-κB nuclear translocation. (A,B) BV2 microglia were treated with 10 μM A53T αSYN in the presence of absence of NP/compounds controls. Cells were fixed and stained with corresponding antibodies. Data are represented as means ± SEM; n = 3. In (A) *P = 0.0147 for αSYN only vs. αSYN + [FAA:TA] NP by one-way ANOVA. In (B), ****P < 0.0001 for NT vs. αSYN only and NT vs. αSYN + [FAA:TA] NP, ***P = 0.0009 for αSYN only vs. αSYN + [FAA:TA] NP by one-way ANOVA. (C) Representative confocal microscopy images showing NF-κB nuclear translocation. Scale bar = 20 μm. (D) [FAA:TA] NPs modulate microglial activation through NF-κB pathway. Intrinsically disordered αSYN protein aggregates upon association with membrane bilayer or certain membrane receptors. Aggregated αSYN has been associated with NF-κB pathway activation, which further leads to the production of pro-inflammatory cytokines and free radicals. By inhibiting intracellular αSYN aggregate formation, NPs may suppress translocation of the key activation mediator (NF-κB p65) involved in αSYN-induced microglial activation. This suppression leads to reduction in downstream pro-inflammatory cytokines TNF-α and IL-6 as well as neurotoxic free radical ROS and NO production.