Rescuing retromer in Parkinson's disease
Both Vp35 p.D620N and LRRK2 pathogenic variants cause late-onset, familial Parkinson's disease. In vivo, we show Vps35 p.D620N activates LRRK2 kinase activity, impairs the recycling and physiologic function of the dopamine transporter (DAT), and can be rescued by LRRK2 kinase inhibitors.