Pharmacological chaperones and lysosomal storage diseases

Low molecular weight pharmacological chaperones newly appear as enzyme enhancement therapy agents in genetic diseases resulting from protein misfolding or mistracking. Certain missense mutations and some small inframe deletions result impair folding, instability and aggregation of polypeptide, altered transport to target subcellular organel/plasma membrane/secretion to extracellular space. They assist proper folding of mutant proteins in endoplasmic reticulum (ER), increase stability, avoid aggregation, increase the activity at their target sites by allowing the mutant protein’s passage from the ER quality control (ERQC) system. Pharmacological chaperones are attracting considerable interest in enhancement of quality of life and clinical improvement at juvenile and adult forms of lysosomal storage diseases which have residual enzymatic activity. In this review, we describe the action mechanism of pharmacological chaperones, the usage area in view of lysosomal storage diseases, chemical chaperones, advantages and disadvantages.