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Genome‐wide screens in yeast reveal that diverse cellular pathways influence the toxicity of various neurodegenerative disease‐associated misfolded proteins
Author(s) -
Cameron Dale Matthew,
Savare Jean,
Higgins Matthew,
Galarza Vicente Sance,
Sia Angela,
Collins Sean,
Shales Michael,
Krogan Nevan,
Farese Robert,
Muchowski Paul,
Weissman Jonathan
Publication year - 2010
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.24.1_supplement.684.1
Subject(s) - neurodegeneration , biology , gene , toxicity , mechanism (biology) , protein aggregation , genome , yeast , genetics , microbiology and biotechnology , disease , chemistry , medicine , philosophy , organic chemistry , epistemology , pathology
A common pathological feature of many fatal neurodegenerative diseases is the formation of neuronal protein aggregates. Despite differences in the composition and localization of the aggregates, the near universality of neuronal protein deposition and neurodegeneration in these diseases suggests the existence of a common pathogenic mechanism related to the aggregation process. To identify cellular pathways that modulate toxicity associated with expression of different disease‐associated proteins, we systematically screened the yeast genome, comprising non‐essential gene deletions and strains in which the levels of essential genes are depleted. We identified a number of genes that enhance or suppress toxicity associated with expression of these proteins. However, rather than illuminating a common mechanism of toxicity, our results suggest that distinct pathways influence the toxicity of each protein. This work was supported by the Larry L. Hillblom Foundation and the National Institutes of Health.