A Neuron-Glial Trans-Signaling Cascade Mediates LRRK2-Induced Neurodegeneration

• DOI: 10.1016/j.celrep.2019.01.077
• Publication Date: 2019-02-12T15:43:27Z
• Authors: Elie Maksoud; Edward H. Liao; A. Pejmun Haghighi
• Keywords: LRRK2; Furin; Neurotoxicity

Pathogenic mutations in leucine-rich repeat kinase 2 (LRRK2) induce an age-dependent loss of dopaminergic (DA) neurons. We have identified Furin 1, a pro-protein convertase, as translational target LRRK2 DA Transgenic knockdown Furin1 or its substrate the bone morphogenic protein (BMP) ligand glass bottom boat (Gbb) protects against LRRK2-induced enhances accumulation phosphorylated Mad (pMad) nuclei glial cells vicinity neurons but not Consistently, exposure to paraquat 1 levels and induces BMP signaling glia. In support neuron-glial model, knocking down pathway members only glia, neurons, can protect toxicity. propose that BMP-signaling cascade is critical for mediating neurodegeneration two models Parkinson's disease, thus opening avenues future therapeutic interventions.