Protein misfolding has been linked to numerous inherited diseases. Loss- and gain-of-function mutations (common features of genetic diseases) may cause the destabilization of proteins, leading to alterations in their properties and/or cellular location, resulting in their incorrect functioning. Misfolded proteins can, however, be rescued via the use of proteostasis regulators and/or pharmacological chaperones, suggesting that treatments with small molecules might be developed for a range of genetic diseases. This work describes the potential of these small molecules in this respect, including for the treatment of congenital disorder of glycosylation (CDG) due to phosphomannomutase 2 deficiency (PMM2-CDG).
Keywords: conformational diseases; congenital disorders of glycosylation; inborn errors of metabolism; misfolding diseases; pharmacological chaperones; protein folding; proteostasis regulators.
© 2017 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.