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).