Next Article in Journal
Physosmotic Induction of Chondrogenic Maturation Is TGF-β Dependent and Enhanced by Calcineurin Inhibitor FK506
Previous Article in Journal
Drug Repositioning for Fabry Disease: Acetylsalicylic Acid Potentiates the Stabilization of Lysosomal Alpha-Galactosidase by Pharmacological Chaperones
Previous Article in Special Issue
α-Arrestins and Their Functions: From Yeast to Human Health
Review

Yeast as a Model to Find New Drugs and Drug Targets for VPS13-Dependent Neurodegenerative Diseases

1
Institute of Biochemistry and Biophysics Polish Academy of Sciences, 02-106 Warsaw, Poland
2
Neuromuscular Unit, Mossakowski Medical Research Institute, Polish Academy of Sciences, 02-106 Warsaw, Poland
*
Author to whom correspondence should be addressed.
Academic Editor: Ian Macreadie
Int. J. Mol. Sci. 2022, 23(9), 5106; https://doi.org/10.3390/ijms23095106
Received: 30 March 2022 / Revised: 28 April 2022 / Accepted: 30 April 2022 / Published: 4 May 2022
Mutations in human VPS13A-D genes result in rare neurological diseases, including chorea-acanthocytosis. The pathogenesis of these diseases is poorly understood, and no effective treatment is available. As VPS13 genes are evolutionarily conserved, the effects of the pathogenic mutations could be studied in model organisms, including yeast, where one VPS13 gene is present. In this review, we summarize advancements obtained using yeast. In recent studies, vps13Δ and vps13-I2749 yeast mutants, which are models of chorea-acanthocytosis, were used to screen for multicopy and chemical suppressors. Two of the suppressors, a fragment of the MYO3 and RCN2 genes, act by downregulating calcineurin activity. In addition, vps13Δ suppression was achieved by using calcineurin inhibitors. The other group of multicopy suppressors were genes: FET4, encoding iron transporter, and CTR1, CTR3 and CCC2, encoding copper transporters. Mechanisms of their suppression rely on causing an increase in the intracellular iron content. Moreover, among the identified chemical suppressors were copper ionophores, which require a functional iron uptake system for activity, and flavonoids, which bind iron. These findings point at areas for further investigation in a higher eukaryotic model of VPS13-related diseases and to new therapeutic targets: calcium signalling and copper and iron homeostasis. Furthermore, the identified drugs are interesting candidates for drug repurposing for these diseases. View Full-Text
Keywords: yeast; chorea-acanthocytosis; VPS13; VPS13A-D; calcium signalling; copper homeostasis; iron homeostasis yeast; chorea-acanthocytosis; VPS13; VPS13A-D; calcium signalling; copper homeostasis; iron homeostasis
Show Figures

Figure 1

MDPI and ACS Style

Kaminska, J.; Soczewka, P.; Rzepnikowska, W.; Zoladek, T. Yeast as a Model to Find New Drugs and Drug Targets for VPS13-Dependent Neurodegenerative Diseases. Int. J. Mol. Sci. 2022, 23, 5106. https://doi.org/10.3390/ijms23095106

AMA Style

Kaminska J, Soczewka P, Rzepnikowska W, Zoladek T. Yeast as a Model to Find New Drugs and Drug Targets for VPS13-Dependent Neurodegenerative Diseases. International Journal of Molecular Sciences. 2022; 23(9):5106. https://doi.org/10.3390/ijms23095106

Chicago/Turabian Style

Kaminska, Joanna, Piotr Soczewka, Weronika Rzepnikowska, and Teresa Zoladek. 2022. "Yeast as a Model to Find New Drugs and Drug Targets for VPS13-Dependent Neurodegenerative Diseases" International Journal of Molecular Sciences 23, no. 9: 5106. https://doi.org/10.3390/ijms23095106

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop