Methods of treating disorders with glycosylation defective proteins
A method of treating a glycosylation-defective protein associated disease or disorder in a subject, the method includes administering to the subject a therapeutically effective amount of a Sarco/ER ATPase (SERCA) inhibitor.
1. A method of treating a glycosylation-defective protein associated disease or disorder in a subject in need thereof, the method comprising:
administering to the subject a therapeutically effective amount of a Sarco/ER ATPase (SERCA) inhibitor.
2. The method of claim 1 , the SERCA inhibitor selected from the group consisting of Artemisinin, Artesunate (Arts), thapsigargin, mipsagargin, DBHQ (2,5-di-tert-butylhydroquinone), Saikosaponin-d (Ssd), SBF-1, ruthenium red, curcumin, F36, gingerol, paxilline, cyclopiazonic acid, sHA14-1, CXL017, and analogs thereof.
3. The method of claim 2 , the SERCA inhibitor comprising Artesunate (Arts).
4. The method of claim 1 , wherein the therapeutically effective amount is the amount required to increase cytosolic calcium levels and perturb ER in cells of the subjects.
5. The method of claim 1 , wherein the therapeutically effective amount is an amount effective to potentiate ER stress and unfolded protein response (UPR) in cells of the subjects.
6. The method of claim 1 , the glycosylation-defective protein associated disease or disorder is a human clarin-1 protein (hCLRN1) defect related disease or disorder.
7. The method of claim 6 , the hCLRN1 defect related disease or disorder comprising a hCLRN1 N48k missense mutation related disease or disorder.
8. The method of claim 7 , the hCLRN1 N48K missense mutation related disease or disorder comprising Usher syndrome type III (USH3).
9. A method of treating a sensory deficit in a subject associated with a mutation of the human clarin-1 protein hCLRN1 protein, the method comprising:
administering to the subject a therapeutically effective amount of a Sarco/ER ATPase (SERCA) inhibitor.
10. The method of claim 9 , the sensory deficit comprising hearing loss.
11. The method of claim 10 , the therapeutically effective amount comprising an amount effective to promote hCLRN1 N48K localization to hair bundles of a hair cell.
12. The method of claim 9 , the SERCA inhibitor selected from the group consisting of Artemisinin, Artesunate (Arts), thapsigargin, mipsagargin, DBHQ (2,5-di-tert-butylhydroquinone), Saikosaponin-d (Ssd), SBF-1, ruthenium red, curcumin, F36, gingerol, paxilline, cyclopiazonic acid, sHA14-1, CXL017, and analogs thereof.
13. The method of claim 9 , the SERCA inhibitor comprising Artesunate (Arts).
14. The method of claim 9 , wherein the SERCA inhibitor is administered prior to sensory deficit in a subject.
15. The method of claim 9 , the sensory deficit associated with the N48K destabilizing missense mutation in the human clarin-1 protein (hCLRN1 N48k ).
16. A method of treating Usher syndrome type III (USH3) in a subject, the method comprising:
administering to the subject a therapeutically effective amount of a Sarco/ER ATPase (SERCA) inhibitor.
17. The method of claim 16 , wherein USH3 is associated with a human clarin-1 protein (hCLRN1) missense mutation.
18. The method of claim 17 , the hCLRN1 missense mutation comprising hCLRN1 N48K .
19. The method of claim 16 , the SERCA inhibitor selected from the group consisting of Artemisinin, Artesunate (Arts), thapsigargin, mipsagargin, DBHQ (2,5-di-tert-butylhydroquinone), Saikosaponin-d (Ssd), SBF-1, ruthenium red, curcumin, F36, gingerol, paxilline, cyclopiazonic acid, sHA14-1, CXL017, and analogs thereof.
20. The method of claim 19 , the SERCA inhibitor comprising Artesunate (Arts).
21. The method of claim 16 , the therapeutically effective amount comprising an amount effective to promote hCLRN1 N48K localization to hair bundles of a hair cell.
22. The method of claim 16 , wherein the SERCA inhibitor is administered prior to sensory deficit in the USH3 subject.