Exacerbating and reversing lysosomal storage diseases: from yeast to humans
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 t...
Saved in:
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Shared Science Publishers OG
2017-08-01
|
| Series: | Microbial Cell |
| Subjects: | |
| Online Access: | http://microbialcell.com/researcharticles/exacerbating-and-reversing-lysosomal-storage-diseases-from-yeast-to-humans/ |
| Tags: |
Add Tag
No Tags, Be the first to tag this record!
|
| _version_ | 1850053089411727360 |
|---|---|
| author | Tamayanthi Rajakumar Andrew B. Munkacsi Stephen L. Sturley |
| author_facet | Tamayanthi Rajakumar Andrew B. Munkacsi Stephen L. Sturley |
| author_sort | Tamayanthi Rajakumar |
| collection | DOAJ |
| description | 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 establish-ment 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. |
| format | Article |
| id | doaj-art-a73662c9a45e43bd8d287ed5b1123fa0 |
| institution | DOAJ |
| issn | 2311-2638 |
| language | English |
| publishDate | 2017-08-01 |
| publisher | Shared Science Publishers OG |
| record_format | Article |
| series | Microbial Cell |
| spelling | doaj-art-a73662c9a45e43bd8d287ed5b1123fa02025-08-20T02:52:37ZengShared Science Publishers OGMicrobial Cell2311-26382017-08-014927829310.15698/mic2017.09.588Exacerbating and reversing lysosomal storage diseases: from yeast to humansTamayanthi Rajakumar0Andrew B. Munkacsi1Stephen L. Sturley2School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand 6012.School of Biological Sciences, Victoria University of Wellington, Wellington, New Zealand 6012.Department of Genetics and Development, Columbia University Medical Center, New York, NY 10032.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 establish-ment 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.http://microbialcell.com/researcharticles/exacerbating-and-reversing-lysosomal-storage-diseases-from-yeast-to-humans/lysosomal storage diseaseNiemann Pick Type-C diseasegene modifierexacerbate-reverseyeastHIVEbola |
| spellingShingle | Tamayanthi Rajakumar Andrew B. Munkacsi Stephen L. Sturley Exacerbating and reversing lysosomal storage diseases: from yeast to humans Microbial Cell lysosomal storage disease Niemann Pick Type-C disease gene modifier exacerbate-reverse yeast HIV Ebola |
| title | Exacerbating and reversing lysosomal storage diseases: from yeast to humans |
| title_full | Exacerbating and reversing lysosomal storage diseases: from yeast to humans |
| title_fullStr | Exacerbating and reversing lysosomal storage diseases: from yeast to humans |
| title_full_unstemmed | Exacerbating and reversing lysosomal storage diseases: from yeast to humans |
| title_short | Exacerbating and reversing lysosomal storage diseases: from yeast to humans |
| title_sort | exacerbating and reversing lysosomal storage diseases from yeast to humans |
| topic | lysosomal storage disease Niemann Pick Type-C disease gene modifier exacerbate-reverse yeast HIV Ebola |
| url | http://microbialcell.com/researcharticles/exacerbating-and-reversing-lysosomal-storage-diseases-from-yeast-to-humans/ |
| work_keys_str_mv | AT tamayanthirajakumar exacerbatingandreversinglysosomalstoragediseasesfromyeasttohumans AT andrewbmunkacsi exacerbatingandreversinglysosomalstoragediseasesfromyeasttohumans AT stephenlsturley exacerbatingandreversinglysosomalstoragediseasesfromyeasttohumans |