Identification of ergothioneine transporter and therapeutic uses thereof
AssigneeUniversität zu Köln
InventorsDirk Gründemann, Edgar Schömig
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Abstract
The transporter that translocates ergothioneine has been identified. Described are methods for identifying and obtaining compounds capable of modulating ergothioneine transport as well as the use of such compounds for the treatment of diseases ergothioneine may be involved in such as autoimmune diseases, in particular rheumatoid arthritis, as well as other diseases arising from cell damage caused by radiation, radicals and relative oxidant species. Furthermore, diagnostic means and methods for determining the presence or susceptibility to such a disease are provided.
Claims77
A method for identifying and/or obtaining a compound capable of modulating ergothioneine transport comprising:
- (a) contacting a test compound with a system for measuring ergothioneine transport activity, which system comprises an ergothioneine transporter (ETT) polypeptide or a functional fragment thereof, and a substrate for measuring ergothioneine transport by the system;
- and
- (b) detecting an altered level of the ergothioneine transport activity of the ETT polypeptide or functional fragment in the presence of the test compound compared to the ergothioneine transport activity in the absence of the test compound and/or presence of a control.
A method for identifying and/or obtaining a compound for the treatment and/or prophylaxis of a disease related to the immune system comprising:
- (a) contacting a test compound with a system for measuring ergothioneine transport activity, which system comprises an ETT polypeptide or a functional fragment thereof, and a substrate for measuring ergothioneine transport by the system;
- and
- (b) detecting an altered level of the ergothioneine transport activity of the ETT polypeptide or functional fragment in the presence of the test compound compared to the ergothioneine transport activity in the absence of the test compound and/or presence of a control.
The method of any one of claims 1 to 7, wherein the substrate for measuring ergothioneine transport is selected from the group consisting of ergothioneine, proline betaine, hydroxyproline betaine or a derivative or analog of any one thereof.
A method for identifying and/or obtaining a compound for treating a disease related to the immune system, which method comprises:
- (a) providing a transgenic animal or a mutant animal, which animal expresses a variant ETT gene, due to which cells or tissue of said animal display a reduced level of ergothioneine compared to cells or tissue of a corresponding wild type or control animal;
- (b) contacting the animal with a test compound;
- and
- (c) detecting an improvement in a condition of the animal in response to the test compound, wherein the condition is a symptom of a disorder of the immune system.
Use of a compound which enhances ergothioneine transport activity of an ETT polypeptide for the manufacture of a medicament for the treatment and/or prophylaxis of a disease related to the immune system.
A kit comprising ergothioneine or a derivative or analog thereof, an ETT polypeptide or functional fragment thereof, a nucleic acid molecule encoding said ETT polypeptide or functional fragment thereof, a sense or antisense molecule derived from said nucleic acid molecule, or an antibody specific for ETT polypeptide;
- and optionally suitable means for detection.
Dependencies are inferred from the claim text.