Small compounds that correct protein misfolding and uses thereof

Abstract

The invention features compositions and methods comprising at least one compound selected from a proteasomal inhibitor, an autophagy inhibitor, a lysosomal inhibitor, an inhibitor of protein transport from the ER to the Golgi, an Hsp90 chaperone inhibitor, a heat shock response activator, a glycosidase inhibitor or histone deacetylase inhibitor that are useful for treating or preventing a protein conformation disease in a subject by correcting misfolded proteins in vivo. The compositions and methods can further comprise an 11-cis-retinal or 9-cis-retinal compound. Examples of protein conformation disorders and / or diseases may include retinitis pigmentosa, age-related macular degeneration, glaucoma, corneal dystrophies, retinoschises, Stargardt's disease, autosomal dominant druzen, Best's macular dystrophy, al -antitrypsin deficiency, cystic fibrosis, Huntington's disease, Parkinson's disease, Alzheimer's disease, nephrogenic diabetes insipidus, cancer and / or Jacob-Creutzfeld disease.

Description

[0001] Cross-Referenced Related Applications [0002] This application claims priority from US Provisional Application No. 60 / 703,068, filed July 27, 2005, the contents of which are incorporated herein by reference. [0003] Statement of Rights to Inventions Made by Federally Sponsored Research Institutes [0004] This work was supported by a grant from the National Eye Institute, grant number EY016070-01. The government may have certain rights in the invention. Background technique [0005] Proteins must fold into the correct three-dimensional conformation to achieve their biological function. The native conformation of a polypeptide is encoded in its primary amino acid sequence, and even a single mutation in an amino acid sequence can impair the protein's ability to assume its proper conformation. When proteins fail to fold properly, their biological and clinical roles are compromised. Aggregation and misfolding of proteins are the main causes of many human diseases, suc...

AI Technical Summary

Problems solved by technology

The native conformation of a polypeptide is encoded in its primary amino acid sequence, and even a single mutation in an amino acid sequence can impair the protein's ability to assume its proper conformation

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