Tuning protein folding in lysosomal storage diseases: the chemistry behind pharmacological chaperones

Misfolding of proteins is the basis of several proteinopathies. Chemical and pharmacological chaperones are small molecules capable of inducing the correct conformation of proteins, thus being of interest for human therapeutics. The most recent developments in medicinal chemistry and in the drug development of pharmacological chaperones are discussed, with focus on lysosomal storage diseases. We review pharmacological chaperones used in lysosomal storage diseases, emphasizing medicinal chemistry approaches and mechanisms of action.