mackenzie-spicer@uiowa.edu
Mentor: Rory Fisher, Ph.D.
Lab Room: 2-505 BSB
Lab Phone: 319-335-8331

Molecular Biology and Signaling of RGS Proteins in Parkinson’s Disease

Parkinson’s disease (PD) is a devastating neurodegenerative disease characterized by the loss of dopaminergic neurons in the substantia nigra pars compacta (SNc) in the midbrain. The mechanisms by which these dopaminergic neurons die and why their loss is associated with aging in PD remains unclear, and although there are treatments that target symptomology, there are no neuroprotective therapies; thus, there is a critical need to further understand the molecular mechanisms causing PD.

The Fisher lab studies regulator of G-protein signaling (RGS) proteins, which are key negative regulators of G protein coupled receptor (GPCR) signaling by virtue of their GTPase-activating protein (GAP) activity toward G protein subunits. GPCR signaling activates a variety of specific second messenger systems that function to control a wide range of important physiological and pathophysiological processes.

Our lab has identified that a specific RGS protein, RGS6, plays a key role in preventing late-age onset of PD. Remarkably, RGS6 is required for the survival of dopaminergic neurons in the SNc, and loss of RGS6 is observed in both mice and human PD studies. Our RGS6 KO mouse model is the first model to recapitulate late-onset PD, which represents the majority of disease cases. Using this model, we seek to elucidate the molecular mechanisms by which RGS6 is regulating dopaminergic neuronal survival and prevention of late-onset PD in hopes of developing neuroprotective strategies for PD.

Ahlers-Dannen KE*, Spicer MM*, and Fisher RA*. (2020). RGS proteins as critical modulators of motor function and their implications in PD. Molecular Pharmacology. *Denotes co-first authors

Luo Z, Ahlers-Dannen KE, Spicer MM, Yang J, Chakravarti B, Alberico S, Stevens HE, Narayanan NS, and Fisher RA. (2019). Age-dependent Nigral Dopaminergic Neurodegeneration and α-Synuclein Accumulation in RGS6-deficient Mice. Journal of Clinical Investigation Insight. pii:126769. doi:10.1172/jci.insight.126769. PubMed PMID: 31120439.

Yang J*, Ahlers-Dannen KE*, Spicer MM, Maity B, Stewart A, Koland JG, and Fisher RA. (2018). RGS6 protein profiling reveals multi-isoformic expression in mouse tissues and a novel brain-specific isoform. In Preparation. *Denotes co-first authors

Hart SL, Spicer MM, Wrynn TE, Chapman TL, Spivey KL, and Gall BG. (2019). Palatability and predator avoidance behavior of salamanders in response to the Virginia Opossum (Didelphis virginiana). American Midland Naturalist, 181(2), 245-258.

Spicer MM, Stokes AN, Chapman TL, Brodie Jr. ED, Brodie III ED, and Gall BG. (2018). An investigation into Tetrodotoxin (TTX) levels associated with the red dorsal spots in Eastern newt (Notophthalmus viridescens) efts and adults. Journal of Toxicology. Article ID 9196865.

Spicer MM, Hart SL, Brighty SR, & Gall BG. (2017). Absence of visual discrimination by female eastern newts during mate selection. Ethology Ecology & Evolution, 29(5), 490-500.

Hart SL, Spicer MM, and Gall BG. (2017). Clutch-level variation in predator avoidance behavior in wood frog (Lithobates sylvaticus) tadpoles. Proceedings of the Indiana Academy of Science. 126: 200-206.