Carboxylic Acid Fullerene (C(60)) Derivatives Attenuated Neuroinflammatory Responses by Modulating Mitochondrial Dynamics

Fullerene (C(60)) derivatives, a unique class of compounds with potent antioxidant properties, have been reported to exert a wide variety of biological activities including neuroprotective properties. Mitochondrial dynamics are an important constituent of cellular quality control and function, and an imbalance of the dynamics eventually leads to mitochondria disruption and cell dysfunctions. This study aimed to assess the effects of carboxylic acid C(60) derivatives (C(60)–COOH) on mitochondrial dynamics and elucidate its associated mechanisms in lipopolysaccharide (LPS)-stimulated BV-2 microglial cell model. Using a cell-based functional screening system labeled with DsRed2-mito in BV-2 cells, we showed that LPS stimulation led to excessive mitochondrial fission, increased mitochondrial localization of dynamin-related protein 1 (Drp1), both of which were markedly suppressed by C(60)–COOH pretreatment. LPS-induced mitochondria reactive oxygen species (ROS) generation and collapse of mitochondrial membrane potential (ΔΨm) were also significantly inhibited by C(60)–COOH. Moreover, we also found that C(60)–COOH pretreatment resulted in the attenuation of LPS-mediated activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK) signaling, as well as the production of pro-inflammatory mediators. Taken together, these findings demonstrated that carboxylic acid C(60) derivatives may exert neuroprotective effects through regulating mitochondrial dynamics and functions in microglial cells, thus providing novel insights into the mechanisms of the neuroprotective properties of carboxylic acid C(60) derivatives.