DISCUSSION
COL-3, a modified tetracycline with non-antibacterial properties [19,38,39], represents a promising molecule to treat neurodegenerative- or inflammation-related diseases, since it is a tetracycline with pleiotropic effects that does not present antibacterial properties and has previous studies demonstrating its safety, toxicity and therapeutic range [40]. In this study, we unveiled COL-3 is a potent inhibitor, in primary microglial cell cultures, of inflammatory reactions prompted by the bacterial cell wall component LPS and by the aggregated form of αS, a potential trigger to PD pathophysiology. COL-3 anti-inflammatory action was observed through TNF-α production/release and Iba-1 expression. Outstandingly, the ability of COL-3 to restrict LPS and αSa-induced microglial inflammation comes, at least partially, from its capacity to inhibit glucose consumption and production of NADPH, the requisite substrate for the superoxide producing enzyme NADPH oxidase. This outcome converts to increased levels of ROS and consequent oxidative stress in the cells, which are also restrained by COL-3 (Figure 7).