Yeast screens for treatment of human disease
AssigneeThe University of Chicago
InventorsSusan Lindquist, Sylvia Krobitsch, Tiago Fleming Outeiro
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Abstract
Screening methods for identifying substances that provide therapeutic value for various diseases associated with protein misfolding are provided. Genetic and chemical screening methods are provided using a yeast system. The methods of the invention provide a rapid and cost-effective method to screen for compounds that prevent protein misfolding and/or protein fibril formation and/or protein aggregation which includes numerous neurodegenerative diseases including Parkinson's disease, Alzheimer's disease, Huntington's disease as well as non-neuronal diseases such as type 2 diabetes.
Claims9
-68. (canceled)
A method of screening for a compound that decreases toxicity associated with ataxin-1, ataxin-2, ataxin-3, ataxin-7, calcium channel, androgen receptor, atrophin-1, SOD 1, immunoglobulin light chain, transthyretin, tau, serum amyloid A, islet amyloid polypeptide, beta2-microglobulin, cystatin-C, gelsolin, or lysozyme, the method comprising:
- providing a yeast cell engineered to express a protein comprising a ataxin-1, ataxin-2, ataxin-3, ataxin-7, calcium channel, androgen receptor, atrophin-1, SOD1, immunoglobulin light chain, transthyretin, tau, serum amyloid A, islet amyloid polypeptide, insulin, beta2-microglobulin, cystatin-C, gelsolin, or lysozyme polypeptide;
- contacting the yeast cell with a candidate compound;
- and
- evaluating the yeast cell for viability, wherein an increase in viability of the yeast cell as compared to viability of the yeast cell in the absence of the candidate compound indicates that the candidate compound decreases toxicity associated with ataxin-1, ataxin-2, ataxin-3, ataxin-7, calcium channel, androgen receptor, atrophin-1, SOD 1, immunoglobulin light chain, transthyretin, tau, serum amyloid A, islet amyloid polypeptide, insulin, beta2-microglobulin, cystatin-C, gelsolin, or lysozyme.
A method of screening for a compound that decreases toxicity associated with ataxin-1, ataxin-2, ataxin-3, ataxin-7, calcium channel, androgen receptor, atrophin-1, SOD 1, immunoglobulin light chain, transthyretin, tau, serum amyloid A, islet amyloid polypeptide, insulin, beta2-microglobulin, cystatin-C, gelsolin, or lysozyme, the method comprising:
- contacting a yeast cell with a candidate compound, wherein the yeast cell expresses a protein comprising a ataxin-1, ataxin-2, ataxin-3, ataxin-7, calcium channel, androgen receptor, atrophin-1, SOD 1, immunoglobulin light chain, transthyretin, tau, serum amyloid A, islet amyloid polypeptide, beta2-microglobulin, cystatin-C, gelsolin, or lysozyme polypeptide;
- contacting the yeast cell with a toxicity inducing agent;
- and
- evaluating the yeast cell for viability, wherein an increase in viability of the yeast cell as compared to viability of the yeast cell in the absence of the candidate compound indicates that the candidate compound decreases toxicity associated with ataxin-1, ataxin-2, ataxin-3, ataxin-7, calcium channel, androgen receptor, atrophin-1, SOD 1, immunoglobulin light chain, transthyretin, tau, serum amyloid A, islet amyloid polypeptide, insulin, beta2-microglobulin, cystatin-C, gelsolin, or lysozyme.
Dependencies are inferred from the claim text.