NLRP3 Inflammasome Activation in a Transgenic Amyotrophic Lateral Sclerosis Model.

Amyotrophic lateral sclerosis (ALS) is a disabling progressive disease characterized by the degeneration of motor neurons, leading to muscle atrophy and paralysis. The majority of cases are sporadic, but also a familiar form of ALS exists, and some genes causative of the pathology were found. In particular, mutations in superoxide dismutase 1 (SOD1) were found in 20% of familiar cases. It is known that neuroinflammation plays a pivotal role in several neurodegenerative disorders, including ALS. Inflammasomes are protein complexes that induce inflammation in response to various stimuli, involved also in neuroinflammation. The NLRP3 inflammasome, which is the best known, after assembly, induces the activation of caspase 1, which in turn activates interleukin (IL)-1β and IL-18. The aim of this work was the evaluation of inflammasome activation in the brain of SOD1 rats, a transgenic model of ALS. We observed the increase in TLR4 and nuclear NF-κB levels in SOD1 rats. Their activation is known as priming signal for inflammasome induction. Moreover, NLRP3 protein increased, associated with the presence of active caspase 1, leading to an increase in IL-18 and IL-1β levels. In addition, IL-1β, IL-18, and IFN-γ amount increased in the spleen of SOD1 rats, together with an increased expression of CD4, CD8, CD44, and CD68 markers. In conclusion, our results showed the activation of the NLRP3 inflammasome in the brain of SOD1 rats, indicating that inflammation plays a main role in ALS.