Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration
Authors:Amit Shrestha1, 2 and Lynn A. Megeney1, 2, 3
doi: 10.15698/mic2015.12.243
Volume 2, pp. 458 to 465, published 26/11/2015.
1 Ottawa Hospital Research Institute, Regenerative Medicine Program, Sprott Centre for Stem Cell Research, The Ottawa Hospital, Ottawa, Ontario, Canada.
2 Department of Cellular and Molecular Medicine University of Ottawa, Ottawa, Ontario, Canada
3 Department of Medicine, University of Ottawa, Ottawa, Ontario, Canada.
Keywords:
yeast, neurodegeneration, proteinopathy, Hsp104, Yca1, TDP-43, α-synuclein
Corresponding Author(s):
Conflict of interest statement:
The author declares no conflict of interest.
Please cite this article as:
Amit Shrestha and Lynn A. Megeney (2015). Yeast proteinopathy models: a robust tool for deciphering the basis of neurodegeneration. Microbial Cell 2(12): 458-465.
© 2015 Shrestha and Megeney. 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:
Protein quality control or proteostasis is an essential determinant of basic cell health and aging. Eukaryotic cells have evolved a number of proteostatic mechanisms to ensure that proteins retain functional conformation, or are rapidly degraded when proteins misfold or self-aggregate. Disruption of proteostasis is now widely recognized as a key feature of aging related illness, specifically neurodegenerative disease. For example, Alzheimer’s disease, Huntington’s disease, Parkinson’s disease and Amyotrophic Lateral Sclerosis (ALS) each target and afflict distinct neuronal cell subtypes, yet this diverse array of human pathologies share the defining feature of aberrant protein aggregation within the affected cell population. Here, we review the use of budding yeast as a robust proxy to study the intersection between proteostasis and neurodegenerative disease. The humanized yeast model has proven to be an amenable platform to identify both, conserved proteostatic mechanisms across eukaryotic phyla and novel disease specific molecular dysfunction. Moreover, we discuss the intriguing concept that yeast specific proteins may be utilized as bona fide therapeutic agents, to correct proteostasis errors across various forms of neurodegeneration.