| First Author | He KJ | Year | 2023 |
| Journal | iScience | Volume | 26 |
| Issue | 11 | Pages | 108130 |
| PubMed ID | 37876795 | Mgi Jnum | J:351289 |
| Mgi Id | MGI:7544665 | Doi | 10.1016/j.isci.2023.108130 |
| Citation | He KJ, et al. (2023) LRRK2 G2019S promotes astrocytic inflammation induced by oligomeric alpha-synuclein through NF-kappaB pathway. iScience 26(11):108130 |
| abstractText | Parkinson's disease (PD) is characterized by the irreversible loss of dopaminergic neurons and the accumulation of alpha-synuclein in Lewy bodies. The oligomeric alpha-synuclein (O-alphaS) is the most toxic form of alpha-synuclein species, and it has been reported to be a robust inflammatory mediator. Mutations in Leucine-Rich Repeat Kinase 2 (LRRK2) are also genetically linked to PD and neuroinflammation. However, how O-alphaS and LRRK2 interact in glial cells remains unclear. Here, we reported that LRRK2 G2019S mutation, which is one of the most frequent causes of familial PD, enhanced the effects of O-alphaS on astrocytes both in vivo and in vitro. Meanwhile, inhibition of LRRK2 kinase activity could relieve the inflammatory effects of both LRRK2 G2019S and O-alphaS. We also demonstrated that nuclear factor kappaB (NF-kappaB) pathway might be involved in the neuroinflammatory responses. These findings revealed that inhibition of LRRK2 kinase activity may be a viable strategy for suppressing neuroinflammation in PD. |
