Modulators of ACYL-COA Lysocardiolipin Acyltransferase 1 (ALCAT1) and Uses Thereof
AssigneeThe Penn State Research Foundation
InventorYuguang Shi
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Abstract
Compositions of modulators of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) expression, function or activity are provided. In particular, inhibitors of ALCAT1 are useful in treating metabolic diseases, cardiac diseases and, in general diseases associated with mitochondrial dysfunction. Assays for identification of novel ALCAT1 modulators are provided.
Claims51
A method of identifying a modulator of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) expression, function or activity, comprising:
- contacting a biological sample with a test agent;
- measuring expression, function or activity of a mitofusin molecule in the biological sample;
- thereby,
- identifying a modulator of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1).
A method of identifying a modulator of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) expression, function or activity, comprising:
- contacting a biological sample with a test agent;
- measuring (a) expression of hypertrophic markers indicative of cardiomyopathy comprising:
- BNP, β-MHC, ANF or ACTA1;
- (b) expression, function or activity of PTEN-induced putative kinase 1 (PINK1);
- thereby,
- identifying the ALCAT1 modulator.
A method of preventing or treating mitochondrial dysfunction in vitro or in vivo, comprising:
- administering to a cell or patient a therapeutically effective amount of an agent that modulates expression, function activity or combinations thereof, of a lysocardiolipin acyltransferase;
- thereby, preventing or treating mitochondrial dysfunction in vitro or in vivo.
A method of preventing or treating mitochondrial dysfunction in vitro or in vivo, comprising:
- administering to a cell or patient a therapeutically effective amount of a mitofusin molecule;
- thereby, preventing or treating mitochondrial dysfunction in vitro or in vivo.
A method of treating a patient suffering from cardiomyopathy or at risk of cardiomyopathy, comprising:
- administering to a patient in need thereof, a therapeutically effective amount of an inhibitor of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1);
- thereby,
- treating a patient suffering from cardiomyopathy.
A method of identifying a modulator of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) expression, function or activity, comprising:
- contacting a biological sample with a test agent;
- measuring expression, function or activity of ALCAT1 molecules in the biological sample;
- thereby,
- identifying a modulator of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1).
A method of identifying a modulator of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) expression, function or activity, comprising:
- contacting a biological sample with a test agent;
- measuring expression of nucleic acid markers or encoded products thereof, indicative of diabetic nephropathy comprising:
- FAS, TNF, TGF-β, DGAT1, CHREBP1, or SREBP1;
- thereby,
- identifying the ALCAT1 modulator.
A method of identifying a modulator of acyl-CoA lysocardiolipin acyltransferase 1 (ALCAT1) expression, function or activity, comprising:
- contacting a biological sample with a test agent;
- measuring expression of nucleic acid markers or encoded products thereof, indicative of fatty liver diseases comprising:
- PPARα, Srebp1c, FAS, ACC1, DGAT1, or CPT1α;
- thereby,
- identifying the ALCAT1 modulator.
Dependencies are inferred from the claim text.