PT - JOURNAL ARTICLE AU - Lin, Yu-En AU - Jaimon, Ebsy AU - Tonelli, Francesca AU - Pfeffer, Suzanne R TI - Pathogenic <em>LRRK2</em> mutations cause loss of primary cilia and Neurturin in striatal parvalbumin interneurons AID - 10.26508/lsa.202402922 DP - 2025 Jan 01 TA - Life Science Alliance PG - e202402922 VI - 8 IP - 1 4099 - https://www.life-science-alliance.org/content/8/1/e202402922.short 4100 - https://www.life-science-alliance.org/content/8/1/e202402922.full SO - Life Sci. Alliance2025 Jan 01; 8 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.