LRRK2-mediated neuroinflammation induced neuronal dysfunctions in a Parkinson's and Alzheimer's disease cellular model

Dissect the transcriptional consequences of neuroinflammation and the role of the kinase LRRK2 in regulating neuronal responses in human induced pluripotent stem cell (hiPSC)-derived neurons exposed to pro-inflammatory conditions relevant to Parkinson's disease (PD) and Alzheimer's disease (AD).Dopaminergic neurons (PD context) and cholinergic neurons (AD context) were differentiated from hiPSCs and subsequently cultured in glial-conditioned medium containing either a-synuclein pre-formed fibrils (a-syn pffs) or amyloid-ß (Aß) fibrils, for PD and aAD respectively. Neuronal cultures were exposed to inflammed media to model chronic inflammatory stress. Overall design: hiPSCs derived dopaminergic neurons were cultured under four experimental conditions: untreated controls (NT; N=4), exposure to a-synuclein pre-formed fibrils (a-syn pffss) for PD context (N=4), treatment with the LRRK2 inhibitor PF (PF; N=5), or treatment with the LRRK2 inhibitor MLi-2 (MLI2; N=4). hiPSCs derived colinergic neurons were cultured under four experimental conditions: untreated controls (NT; N=5), exposure to amyloid-ß (Aß) for AD context (N=5), treatment with the LRRK2 inhibitor PF (PF; N=5), or treatment with the LRRK2 inhibitor MLi-2 (MLI2; N=5).