Methods of identifying agents that modulate mitochondrial function
AssigneeThe J. David Gladstone Institutes
InventorsYadong Huang, Jens Brodbeck
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Abstract
The present invention provides isolated cells comprising a nucleic acid encoding a toxic form of apoE. The present invention further provides screening methods for identifying compounds that reduce apoE-induced impairment of mitochondrial integrity and/or function. The present invention further provides kits for use in carrying out a subject screening method. The present invention provides agents that reduce apoE-induced impairment of mitochondrial integrity and/or function; and use of such agents in the treatment of apoE-related disorders.
Claims21
A method of identifying an agent that reduces apolipoprotein E (apoE) neurotoxic polypeptide-induced impairment of mitochondrial integrity and/or function, the method comprising:
- contacting a eukaryotic cell with a test agent, wherein the eukaryotic cell comprises in the cytosol a toxic apoE polypeptide, and wherein the eukaryotic cell comprises in a mitochondrion an indicator polypeptide that provides a detectable signal;
- and
- determining the effect, if any, of the test agent on mitochondrial integrity and/or function, wherein a reduction in apoE-induced impairment of mitochondrial integrity and/or function, compared to mitochondrial integrity and/or function in the absence of the test agent, indicates that the test agent reduces apoE-induced impairment of mitochondrial integrity and/or function.
An isolated eukaryotic cell comprising:
- a nucleic acid comprising a nucleotide sequence encoding a toxic apolipoprotein E polypeptide, wherein the nucleotide sequence is operably linked to a promoter;
- and
- a nucleic acid comprising a nucleotide sequence encoding:
- i) an indicator polypeptide that provides a detectable signal;
- and ii) a mitochondrial localization signal fused to the indicator.
Dependencies are inferred from the claim text.