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Methods for identifying agents that inhibit serum aging factors and uses and compositions thereof

a technology of serum aging factors and identifying agents, which is applied in the field of mitochondrial theory of aging, can solve the problems of difficult linkage between mtdna alterations and other forms of cellular and tissue changes related to aging, and the alterations of mtdna of itself, and achieve the effect of inhibiting the reaction of ar—nox with other substrates and decreasing the ability of ar—nox to genera

Inactive Publication Date: 2005-08-04
PURDUE RES FOUND INC
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  • Abstract
  • Description
  • Claims
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AI Technical Summary

Benefits of technology

The present invention provides pharmaceutical compositions, methods, and kits for treating disorders caused by oxidative changes in cells that lead to aging. The invention targets an aging-related isoform of NADH oxidase (AR—NOX) shed into the sera by aging cells. Ubiquinones, which inhibit the activity of AR—NOX, reduce the generation of reactive oxygen species and the resulting oxidative damage. The invention also includes methods for screening assays to identify agents that sequester AR—NOX and various modes of administration of compounds that sequester AR—NOX. The invention also includes the isolation and characterization of AR—NOX.

Problems solved by technology

However, alterations of mtDNA of themselves have been difficult to link to other forms of cellular and tissue changes related to aging.
Nevertheless, alterations of mtDNA and other forms of cellular and tissue changes, related to aging, have been difficult to link.

Method used

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  • Methods for identifying agents that inhibit serum aging factors and uses and compositions thereof
  • Methods for identifying agents that inhibit serum aging factors and uses and compositions thereof
  • Methods for identifying agents that inhibit serum aging factors and uses and compositions thereof

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Embodiment Construction

[0033] The present invention provides pharmaceutical compositions, methods of use, and pharmaceutial kits for the treatment of disorders resulting from oxidative changes in cells that result in aging by targeting an aging-related isoform of NADH oxidase (AR—NOX), shed into the sera by aging cells.

[0034] The invention is based in part, on the Inventors' discovery that ubiquinones inhibit the activity of an aging-related isoform of NADH oxidase (AR—NOX) shed into the sera by aging cells. The inhibition of this hyperactive form of NOX, AR—NOX, by ubiquinones results in a decrease in the generation of reactive oxygen species by AR—NOX. A decrease in reactive oxygen species should result in a decrease of oxidative damage resulting from said reactive oxygen species.

5.1. Plasma Membrane Hydroquinone (NADH) Oxidase (NOX)

[0035] The plasma membrane NADH oxidase (NOX) is a unique cell surface protein with hydroquinone (NADH) oxidase and protein disulfide-thiol interchange activities that no...

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Abstract

The invention described herein encompasses methods of preventing or treating disorders caused by oxidative damage by an aging-specific isoform of NADH oxidase (AR—NOX). The invention encompasses methods of assaying, screening, and identifying agents that inhibit AR—NOX, as well as methods using ubiquinone to inhibit the ability of AR—NOX to generate reactive oxygen species. These agents may be formulated into pharmaceutical compositions in the prevention and treatment of disorders caused by oxidative damage.

Description

[0001] This application claims benefit of U.S. provisional application serial No. 60 / 126,894 filed Mar. 30, 1999.1. INTRODUCTION [0002] The present invention relates to methods for the prevention or treatment of disorders and complications of disorders resulting from cell damage caused by an aging-related isoform of NADH oxidase (AR—NOX). The invention comprises assays for screening for agents that bind AR—NOX and inhibit the ability of AR—NOX to generate reactive oxygen species as well as methods of using ubiquinone to inhibit the ability of AR—NOX to generate reactive oxygen species. The invention also encompasses using the therapeutic compounds detected in the screening assays of the invention in a pharmaceutically acceptable carrier. 2. BACKGROUND OF THE INVENTION 2.1. Mitochondrial Theory of Aging [0003] The mitochondrial theory of aging proposes that accumulation of spontaneous somatic mutations of mitochondrial DNA (mtDNA) leads to errors of mtDNA-encoded polypeptide chains (...

Claims

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Application Information

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Patent Type & Authority Applications(United States)
IPC IPC(8): A61K31/122
CPCA61K31/122Y02A50/30
Inventor MORRE, DOROTHY M.MORRE, D. JAMES
Owner PURDUE RES FOUND INC
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