5 Discussion
In conclusion, our work demonstrated for the first time in primary cortical neuronal culture an anti-inflammatory and neuroprotective effect of the α-Klotho protein as the citotoxiciyty of GCM could be rescued by α-Klotho pretreatment (GCM-KL). This neuroprotective α-Klotho effect is at least partially mediated by astrocyte NF-κB modulation of neuroinflammation. These data suggest that α-Klotho can act not just in the metabolic coupling between neurons and astrocytes (Mazucanti, Kawamoto et al., 2019), but it is also an important player in modulating neuroinflammation which is important to integrate insulin and glutamate action in neurons. Thus, α-Klotho’s therapeutic potential is evidenced in pathological processes that have a neuroinflammatory component.