Molecular cross-talk between Lrrk2 and NF-κ/INS;B in neuroinflammation in an/INS; animal model of Parkinson's disease (PD)

Background: Alteration or mutation of /INS;LRRK2, /INS;highly expressed in microglia and neurons has been implicated to PD. It was found that LRRK2 deficiency attenuated LPS-induced mRNA and/or protein expression of cytokines and NF-κB was decreased in LRRK2-knock down cells. LRRK2-induced NF-κB activation was dependent on the /INS;IKK complex, because it was inhibited by a dominant negative form of IKK. The main PD-associated mutant LRRK2-G2019S did not activate NF-κB differently from wild-/INS;type protein. It is not clear whether PD-LRRK2 mutations operate through a gain or loss of function that might act in a dominant negative fashion, recruiting and neutralizing wild-type proteins.