Pharmacological Chaperones: Design and Development of New Therapeutic Strategies for the Treatment of Conformational Diseases.
Errors in protein folding may result in premature clearance of structurally aberrant proteins, or in the accumulation of toxic misfolded species or protein aggregates. These pathological events lead to a large range of conditions known as conformational diseases. Several research groups have presented possible therapeutic solutions for their treatment by developing novel compounds, known as pharmacological chaperones. These cell-permeable molecules selectively provide a molecular scaffold around which misfolded proteins can recover their native folding and, thus, their biological activities. Here, we review therapeutic strategies, clinical potentials, and cost-benefit impacts of several classes of pharmacological chaperones for the treatment of a series of conformational diseases.
Department of Biochemistry and Biophysics, University of North Carolina , 120 Mason Farm Road, Chapel Hill, North Carolina 27599, United States.
Marino
M
Convertino
Department of Biochemistry and Biophysics, University of North Carolina , 120 Mason Farm Road, Chapel Hill, North Carolina 27599, United States.
Jhuma
J
Das
Department of Biochemistry and Biophysics, University of North Carolina , 120 Mason Farm Road, Chapel Hill, North Carolina 27599, United States.
Nikolay V
NV
Dokholyan
D000544:Alzheimer Disease / Q000188:drug therapy; D000818:Animals; D053327:Apolipoprotein E4 / Q000737:chemistry / Q000378:metabolism; D003550:Cystic Fibrosis / Q000188:drug therapy; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000737:chemistry / Q000378:metabolism; D006801:Humans; D008024:Ligands; D016464:Lysosomal Storage Diseases / Q000188:drug therapy; D011228:Prealbumin / Q000737:chemistry / Q000378:metabolism; D058849:Protein Refolding / Q000187:drug effects*; D057165:Proteostasis Deficiencies / Q000188:drug therapy*; D017465:Receptors, Opioid, delta / Q000737:chemistry / Q000378:metabolism; D000519:alpha-Galactosidase / Q000737:chemistry / Q000378:metabolism; D001616:beta-Galactosidase / Q000737:chemistry / Q000378:metabolism; D001617:beta-Glucosidase / Q000737:chemistry / Q000378:metabolism
D053327:Apolipoprotein E4; D008024:Ligands; D011228:Prealbumin; D017465:Receptors, Opioid, delta; D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D001617:beta-Glucosidase; D000519:alpha-Galactosidase; D001616:beta-Galactosidase