Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2driven and idiopathic Parkinson’s disease

Activating LRRK2 mutations cause Parkinson’s disease. Previously, we showed that cholinergic interneurons and astrocytes but not medium spiny neurons of the dorsal striatum lose primary cilia in LRRK2 mutant mice. Single nucleus RNA sequencing shows that cilia loss in cholinergic interneurons correlates with higher LRRK2 expression and decreased glial derived neurotrophic factor transcription. Nevertheless, much higher LRRK2 expression is seen in medium spiny neurons that have normal cilia in mice and humans. In parallel with decreased striatal dopaminergic neurite density, LRRK2 G2019S neurons show increased autism-linked CNTN5 adhesion protein expression; glial cells show significant loss of ferritin heavy chain. Human striatal tissue from LRRK2 pathway mutation carriers and idiopathic Parkinson’s disease show similar cilia loss in cholinergic interneurons and astrocytes and overall loss of such neurons. These data strongly suggest that loss of cilia in specific striatal cell types de..., Collection/generation of RNA sequencing data: Mice were PBS perfused and brains were removed by surgical dissection. Dorsal striatal tissue was isolated in ice cold PBS using a light dissection micrscope. Striatal tissues were placed in 1.5 mL eppendorf tubes and quickly frozen in a 50:50 slurry containing 200 proof ethanol and dry ice.  1 mL of cold homogenization buffer was added and the samples were transferred to dounce homogenizers. The samples were dounced 10 times with the loose pestle and 10 times with the tight pestle on ice.  Homogenates were transferred to a conical tube through 30um strainers to remove large debris. Tubes were spun for 10 minutes at 4 C, 900xg. Supernatant was removed with only ~50 µL of solution remaining.  Samples were resuspended in 450 µL of blocking buffer. 10 µL of each sample was combined with 10 µL 0.4% Trypan Blue to assess nuclei quality and sample yield using a hemocytometer. Concentrations were adjusted to 1000 nuclei/µL. The Stanford Genomics ce..., , # Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2driven and idiopathic Parkinson’s disease

[https://doi.org/10.5061/dryad.pk0p2ngvp](https://doi.org/10.5061/dryad.pk0p2ngvp)

**General Information**

Title of Dataset: Loss of primary cilia and dopaminergic neuroprotection in pathogenic LRRK2driven and idiopathic Parkinson’s disease

Author/Principal Investigator Information
Name: Suzanne Pfeffer
ORCID: 0000-0002-6462-984X
Institution: Stanford University
Address: Beckman Center Room B413
279 Campus Drive
Stanford, California 94305-5307
Email: [[e-mail]](mailto:[e-mail])
Author/Associate or Co-investigator Information

Name: Shahzad Khan
ORCID:0000-0003-3962-0226
Present Institution: University of North Carolina at Chapel Hill
Address: Beckman Center Room B453
279 Campus Drive
Stanford, California 94305-5307
Email: [[e-mail]](mailto:[e-mail])
Date of data collection: 2022-01-12
Geographic location of data co...