Protein misfolding is characterized by the inability of proteins to achieve or
maintain their bioactive conformation. In addition to protein mutation, intracellular
factors such as pH changes, metal ions, and oxidative stress contribute to protein
misfolding. To modulate the level of misfolded proteins, different approaches are
feasible including the use of pharmacological or chemical chaperones, the activation of
degradative pathways and the manipulation of natural folding mechanism. Errors in
protein folding are correlated to a broad range of diseases, from common allergies to
neurodegenerative diseases, and at the moment, many examples exist of the successful
control of protein unfolding that may be used in the therapy of these disorders. This
chapter gives an overview on small molecules that can be used to stabilize protein,
helping it to achieve near-native conformation and bring back its functions with an
emphasis on pharmacological and chemical chaperones.
Keywords: Osmolytes, Pharmacological chaperones, Protein misfolding diseases,
Small molecules.
