Neurite Aggregation and Calcium Dysfunction in iPSC-Derived Sensory Neurons with Parkinson's Disease-Related LRRK2 G2019S Mutation. Stem Cell Reports 2015 Dec 08;5(6):1039-1052
Date
12/15/2015Pubmed ID
26651604Pubmed Central ID
PMC4682343DOI
10.1016/j.stemcr.2015.11.004Scopus ID
2-s2.0-84949513552 (requires institutional sign-in at Scopus site) 75 CitationsAbstract
Mutations in leucine-rich repeat kinase 2 (LRRK2) are the most-common genetic determinants of Parkinson's disease (PD). The G2019S mutation is detected most frequently and is associated with increased kinase activity. Whereas G2019S mutant dopamine neurons exhibit neurite elongation deficits, the effect of G2019S on other neuronal subtypes is unknown. As PD patients also suffer from non-motor symptoms that may be unrelated to dopamine neuron loss, we used induced pluripotent stem cells (iPSCs) to assess morphological and functional properties of peripheral sensory neurons. LRRK2 G2019S iPSC-derived sensory neurons exhibited normal neurite length but had large microtubule-containing neurite aggregations. Additionally, LRRK2 G2019S iPSC-derived sensory neurons displayed altered calcium dynamics. Treatment with LRRK2 kinase inhibitors resulted in significant, but not complete, morphological and functional rescue. These data indicate a role for LRRK2 kinase activity in sensory neuron structure and function, which when disrupted, may lead to sensory neuron deficits in PD.
Author List
Schwab AJ, Ebert ADAuthor
Allison D. Ebert PhD Center Director, Professor in the Cell Biology, Neurobiology and Anatomy department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
CalciumCell Line
Humans
Induced Pluripotent Stem Cells
Leucine-Rich Repeat Serine-Threonine Protein Kinase-2
Microtubules
Neurites
Neurogenesis
Parkinson Disease
Point Mutation
Sensory Receptor Cells
