Abstract
A pharmacoperone (from "pharmacological chaperone") is a small molecule that enters cells and serves as molecular scaffolding in order to cause otherwise-misfolded mutant proteins to fold and route correctly within the cell. Pharmacoperones have broad therapeutic applicability since a large number of diseases have their genesis in the misfolding of proteins and resultant misrouting within the cell. Misrouting may result in loss-of-function and, potentially, the accumulation of defective mutants in cellular compartments. Most known pharmacoperones were initially derived from receptor antagonist screens and, for this reason, present a complex pharmacology, although these are highly target specific. In this summary, we describe efforts to produce high throughput screens that identify these molecules from chemical libraries as well as a mouse model which provides proof-of-principle for in vivo protein rescue using existing pharmacoperones.
Original language | English (US) |
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Pages (from-to) | 38-51 |
Number of pages | 14 |
Journal | Pharmacological Research |
Volume | 83 |
DOIs | |
State | Published - May 2014 |
Keywords
- Animal models
- High throughput screens
- Pharmacoperone
- Protein rescue
- Protein trafficking
- Therapeutic approaches
ASJC Scopus subject areas
- Pharmacology