Dysregulated phosphorylation of Rab GTPases by LRRK2 induces neurodegeneration.

Ga Ram JeongEun-Hae JangJae Ryul BaeSoyoung JunHo Chul KangChi-Hu ParkJoo-Ho ShinYukio YamamotoKeiko Tanaka-YamamotoValina L DawsonTed M DawsonEun-Mi HurByoung Dae Lee

Published in: Molecular neurodegeneration (2018)

Here we show that a subset of Rab GTPases are authentic substrates of LRRK2 both in vitro and in cells. We also provide evidence that dysregulation of Rab phosphorylation in the LRRK2 site induces neurotoxicity in primary neurons and degeneration of dopaminergic neurons in vivo. Our study suggests that Rab GTPases might mediate LRRK2 toxicity in the progression of PD.

Keyphrases

spinal cord
induced apoptosis
oxidative stress
signaling pathway
endoplasmic reticulum stress
pi k akt