title: Chemical and/or biological therapeutic strategies to ameliorate protein misfolding diseases.
abstract: Inheriting a mutant misfolding-prone protein that cannot be efficiently folded in a given cell type(s) results in a spectrum of human loss-of-function misfolding diseases. The inability of the biological protein maturation pathways to adapt to a specific misfolding-prone protein also contributes to pathology. Chemical and biological therapeutic strategies are presented that restore protein homeostasis, or proteostasis, either by enhancing the biological capacity of the proteostasis network or through small molecule stabilization of a specific misfolding-prone protein. Herein, we review the recent literature on therapeutic strategies to ameliorate protein misfolding diseases that function through either of these mechanisms, or a combination thereof, and provide our perspective on the promise of alleviating protein misfolding diseases by taking advantage of proteostasis adaptation.
authors.affiliation: Departments of Chemistry and Molecular and Experimental Medicine and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, United States.
authors.forename: Derrick Sek Tong
authors.initials: DS
authors.lastname: Ong
authors.forename: Jeffery W
authors.initials: JW
authors.lastname: Kelly
mesh_terms: D000818:Animals; D004721:Endoplasmic Reticulum / Q000378:metabolism; D006801:Humans; D017510:Protein Folding; D021381:Protein Transport; D011506:Proteins / Q000737:chemistry / Q000378:metabolism; D057165:Proteostasis Deficiencies / Q000628:therapy*; D013312:Stress, Physiological
chemical_list: D011506:Proteins