TY - JOUR
T1 - Chemical and/or biological therapeutic strategies to ameliorate protein misfolding diseases
AU - Ong, Derrick Sek Tong
AU - Kelly, Jeffery W.
N1 - Funding Information:
We thank Dr. Colleen Fearns for critical feedback on this review. This work was supported by the NIH ( DK75295 ), the Skaggs Institute for Chemical Biology, and the Lita Annenberg Hazen Foundation.
PY - 2011/4
Y1 - 2011/4
N2 - 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.
AB - 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.
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U2 - 10.1016/j.ceb.2010.11.002
DO - 10.1016/j.ceb.2010.11.002
M3 - Review article
C2 - 21146391
AN - SCOPUS:79954416821
SN - 0955-0674
VL - 23
SP - 231
EP - 238
JO - Current Opinion in Cell Biology
JF - Current Opinion in Cell Biology
IS - 2
ER -