Inhibition of LRRK2 Kinase Activity with a Novel Inhibitor (CS 82) Inhibits NLRC4 Inflammasome Activation and Reduces Intestinal Inflammation Severity

Abstract In the last twenty years Leucine Rich Repeat Kinase 2 (LRRK2) has received immense attention due to its association with several diseases, for example, neurodegenerative disease PD (Parkinson’s Disease), inflammatory bowel (IBD), Crohn’s (CD), infectious Leprosy etc. Not only do genetic mutations make this protein a hotspot various diseases but also it shows some pleotropic characteristics which might influence diseases. LRRK2 directly controls proteins example Rab GTPase proteins, NLRC4 inflammasomes showed correlation auto-inflammatory such as CD, Macrophage Activation Syndrome (MAS) Here we report that dependent cytokine storm retarded through kinase inhibition well reduces severity of intestinal inflammation. For novel inhibitor (Termed CS 82) been used. vitro studies disclosed suppress phosphorylation ability phosphorylate targets, 10 and 12; in addition, they human dendritic cell production TNFa stimulated by known activators including Dectin-1-ligand, zymosan- depleted S. cerevisiae extract. Finally, inhibitors exhibited powerful suppression mediate inflammasome IL-1beta. deficiency no effect on IL-1b productions. These findings suggest activity activation productions inflammation severity.