LRRK2-NFATc2 Pathway Associated with Neuroinflammation May Be a Potential Therapeutic Target for Parkinson’s Disease

Figures & data

Figure 1 Neuron-released α-synuclein activated microglia through TLR2, and subsequently activated LRRK2 kinase. NFATc2, as a kinase substrate of LRRK2, was directly phosphorylated, which accelerated nuclear translocation of NFATc2 where cytokine/chemokine gene expression such as IL-6 and TNF-α, were upregulated by NFATc2 transcriptional activity. This resulted in a neurotoxic inflammatory environment, which in return aggravated the neuronal degeneration in a mouse model of PD. Data from Kim et al.¹⁵

Kim C, Beilina A, Smith N, et al. LRRK2 mediates microglial neurotoxicity via NFATc2 in rodent models of synucleinopathies. Sci Transl Med. 2020;12:12. doi:10.1126/scitranslmed.aay0399

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