Method and compositions for treatment of calcineurin-related diseases

摘要

Therapeutic compositions for treatment of protein serine/threonine phosphatase-related diseases are obtained by engineering amino acid sequences that disrupt interaction between the protein serine/threonine phosphatase and a protein inhibitor and are provided herein. Calcineurin and PPI are examples of protein serine/threonine phosphatases. RCAN1 is an inhibitor of calcineurin and is overexpressed in patients with serious diseases, such as Down syndrome and Alzheimer's disease. Molecules that bind RCAN1 at regions that interact with calcineurin selectively modulate functions of calcineurin to treat these diseases. Methods of treating a subject for a protein serine/threonine phosphatase-related disease by administering a molecule having an amino acid sequence selected from the group of SEQ ID NOs: 1-19 are further provided.

主权项

1. A method for treating a protein serine/threonine phosphatase-related disease, the method comprising the steps of:
administering to the subject a composition that disrupts interaction between a protein inhibitor RCAN1 (SEQ ID NO:1) and a protein serine/threonine phosphatase calcineurin in the subject, wherein the protein inhibitor inhibits at least one function of the calcineurin protein serine/threonine phosphatase, wherein the composition comprises a peptide comprising an amino acid sequence selected from the group of SEQ ID nos: 3, 5, 7, 8, 13, and 14; increasing the function of the calcineurin protein serine/threonine phosphatase compared to the function prior to the administering and decreasing a symptom of the calcineurin protein serine/threonine phosphatase-related disease; thereby treating the subject for the disease wherein the disease is Down syndrome or type II diabetes.