RT Journal Article SR Electronic T1 Pathogenic LRRK2 mutations cause loss of primary cilia and Neurturin in striatal parvalbumin interneurons JF Life Science Alliance JO Life Sci. Alliance FD Life Science Alliance LLC SP e202402922 DO 10.26508/lsa.202402922 VO 8 IS 1 A1 Lin, Yu-En A1 Jaimon, Ebsy A1 Tonelli, Francesca A1 Pfeffer, Suzanne R YR 2025 UL https://www.life-science-alliance.org/content/8/1/e202402922.abstract AB Parkinson’s disease–associated, activating mutations in the LRRK2 kinase block primary cilium formation in cell culture and in specific cell types in the brain. In the striatum that is important for movement control, about half of astrocytes and cholinergic interneurons, but not the predominant medium spiny neurons, lose their primary cilia. Here, we show that mouse and human striatal parvalbumin interneurons that are inhibitory regulators of movement also lose primary cilia. Without cilia, these neurons are not able to respond to Sonic hedgehog signals that normally induce the expression of Patched RNA, and their numbers decrease. In addition, in mouse, glial cell line–derived neurotrophic factor–related Neurturin RNA is significantly decreased. These experiments highlight the importance of parvalbumin neurons in cilium-dependent, neuroprotective signaling pathways and show that LRRK2 activation correlates with decreased Neurturin production, resulting in less neuroprotection for dopamine neurons.All primary data are available at Yu-En et al (2024); https://doi.org/10.5061/dryad.z08kprrpx and Lin et al (2024); https://doi.org/10.5281/zenodo.11510059.