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Article

Glitazone Treatment Rescues Phenotypic Deficits in a Fly Model of Gaucher/Parkinson’s Disease

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Elson S. Floyd College of Medicine, Washington State University, Spokane, WA 99202, USA
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Steve Gleason Institute for Neuroscience, Washington State University, Spokane, WA 99202, USA
*
Author to whom correspondence should be addressed.
Academic Editors: Serge Birman, Emi Nagoshi and Frank Hirth
Int. J. Mol. Sci. 2021, 22(23), 12740; https://doi.org/10.3390/ijms222312740
Received: 8 October 2021 / Revised: 19 November 2021 / Accepted: 23 November 2021 / Published: 25 November 2021
Parkinson’s Disease (PD) is the most common movement disorder, and the strongest genetic risk factor for PD is mutations in the glucocerebrosidase gene (GBA). Mutations in GBA also lead to the development of Gaucher Disease (GD), the most common type of lysosomal storage disorder. Current therapeutic approaches fail to address neurological GD symptoms. Therefore, identifying therapeutic strategies that improve the phenotypic traits associated with GD/PD in animal models may provide an opportunity for treating neurological manifestations of GD/PD. Thiazolidinediones (TZDs, also called glitazones) are a class of compounds targeted for the treatment of type 2 diabetes, and have also shown promise for the treatment of neurodegenerative disease, including PD. Here, we tested the efficacy of glitazone administration during development in a fly GD model with deletions in the GBA homolog, dGBA1b (GBA1ΔTT/ΔTT). We observed an optimal dose of pioglitazone (PGZ) at a concentration of 1 μM that reduced sleep deficits, locomotor impairments, climbing defects, and restoration of normal protein levels of Ref(2)P, a marker of autophagic flux, in GBA1ΔTT/ΔTT mutant flies, compared to GBA1+/+ control flies. These data suggest that PGZ may represent a potential compound with which to treat GD/PD by improving function of lysosomal-autophagy pathways, a cellular process that removes misfolded or aggregated proteins. View Full-Text
Keywords: neurodegeneration; autophagy; Lewy body; dementia; p62; β-acid glucosidase 1 neurodegeneration; autophagy; Lewy body; dementia; p62; β-acid glucosidase 1
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MDPI and ACS Style

Shola-Dare, O.; Bailess, S.; Flores, C.C.; Vanderheyden, W.M.; Gerstner, J.R. Glitazone Treatment Rescues Phenotypic Deficits in a Fly Model of Gaucher/Parkinson’s Disease. Int. J. Mol. Sci. 2021, 22, 12740. https://doi.org/10.3390/ijms222312740

AMA Style

Shola-Dare O, Bailess S, Flores CC, Vanderheyden WM, Gerstner JR. Glitazone Treatment Rescues Phenotypic Deficits in a Fly Model of Gaucher/Parkinson’s Disease. International Journal of Molecular Sciences. 2021; 22(23):12740. https://doi.org/10.3390/ijms222312740

Chicago/Turabian Style

Shola-Dare, Oluwanifemi, Shelby Bailess, Carlos C. Flores, William M. Vanderheyden, and Jason R. Gerstner 2021. "Glitazone Treatment Rescues Phenotypic Deficits in a Fly Model of Gaucher/Parkinson’s Disease" International Journal of Molecular Sciences 22, no. 23: 12740. https://doi.org/10.3390/ijms222312740

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