Odetta Antico

Editor’s summary Mutations in the kinase LRRK2 associated with Parkinson’s disease (PD) cause the loss of cilia in cells in the striatum of the brain, disrupting a signaling circuit that is critical to the survival of dopaminergic neurons in the substantia nigra. Jaimon et al. tested the LRRK2 inhibitor MLi-2 in a mouse model of early stage, LRRK2 mutation–associated PD.

eLife assessment This is a useful manuscript describing the competitive binding between Parkin domains to define the importance of dimerization in the mechanism of Parkin regulation and catalytic activity.

Abstract Parkinson’s disease-associated, activating mutations in Leucine Rich Repeat Kinase 2 (LRRK2) block primary cilia formation in cholinergic and parvalbumin interneurons and astrocytes in the striatum, decreasing the production of GDNF and NRTN neuroprotective factors that normally support dopaminergic neuron viability.