Exacerbating and reversing lysosomal storage diseases: from yeast to humans
Authors:Tamayanthi Rajakumar1, Andrew B. Munkacsi1,2 and Stephen L. Sturley3
doi: 10.15698/mic2017.09.588
Volume 4, pp. 278 to 293, published 25/08/2017.
1 School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand 6012.
2 Centre for Biodiscovery, Victoria University of Wellington, Wellington, New Zealand 6012.
3 Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.
Keywords:
lysosomal storage disease, Niemann Pick Type-C disease, gene modifier, exacerbate-reverse, yeast, HIV, Ebola.
Corresponding Author(s):
Conflict of interest statement:
The authors report no conflict of interest.
Please cite this article as:
Tamayanthi Rajakumar, Andrew B. Munkacsi, and Stephen L. Sturley (2017). Exacerbating and reversing lysosomal storage diseases: from yeast to humans. Microbial Cell 4(9): 278-293. doi: 10.15698/mic2017.09.588
© 2017 Rajakumar et al. This is an open-access article released under the terms of the Creative Commons Attribution (CC BY) license, which allows the unrestricted use, distribution, and reproduction in any medium, provided the original author and source are acknowledged.
Abstract:
Lysosomal storage diseases (LSDs) arise from monogenic deficiencies in lysosomal proteins and pathways and are characterized by a tissue-wide accumulation of a vast variety of macromolecules, normally specific to each genetic lesion. Strategies for treatment of LSDs commonly depend on reduction of the offending metabolite(s) by substrate depletion or enzyme replacement. However, at least 44 of the ~50 LSDs are currently recalcitrant to intervention. Murine models have provided significant insights into our understanding of many LSD mechanisms; however, these systems do not readily permit phenotypic screening of compound libraries, or the establishment of genetic or gene-environment interaction networks. Many of the genes causing LSDs are evolutionarily conserved, thus facilitating the application of models system to provide additional insight into LSDs. Here, we review the utility of yeast models of 3 LSDs: Batten disease, cystinosis, and Niemann-Pick type C disease. We will focus on the translation of research from yeast models into human patients suffering from these LSDs. We will also discuss the use of yeast models to investigate the penetrance of LSDs, such as Niemann-Pick type C disease, into more prevalent syndromes including viral infection and obesity.