Dominant-negative effects of LRRK2 heterodimers: A possible mechanism of neurodegeneration in Parkinson's disease caused by LRRK2 I2020T mutation

► WT LRRK2 is degraded by WT LRRK2/I2020T LRRK2 (WT/IT)-heterodimer formation. ► Anti-apoptotic protectivity of LRRK2 is impaired by WT/IT-heterodimer formation. ► Akt1 phosphorylation activity of LRRK2 is impaired by WT/IT-heterodimer formation. ► I2020T mutation causes dominant-negative effect on neurodegeneration.