Parkinson's disease (PD) is characterized by the irreversible loss of dopaminergic neurons and the accumulation of α-synuclein in Lewy bodies. The oligomeric α-synuclein (O-αS) is the most toxic form of α-synuclein species, and it has been reported to be a robust inflammatory mediator. Mutations in () are also genetically linked to PD and neuroinflammation. However, how O-αS and LRRK2 interact in glial cells remains unclear. Here, we reported that mutation, which is one of the most frequent causes of familial PD, enhanced the effects of O-αS on astrocytes both and . Meanwhile, inhibition of LRRK2 kinase activity could relieve the inflammatory effects of both and O-αS. We also demonstrated that nuclear factor κB (NF-κB) pathway might be involved in the neuroinflammatory responses. These findings revealed that inhibition of kinase activity may be a viable strategy for suppressing neuroinflammation in PD.