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Small Molecules, Chaperones and Neurodegenerative Disease
Author(s) -
Gestwicki Jason E
Publication year - 2008
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.22.1_supplement.1055.1
Subject(s) - co chaperone , protein folding , small molecule , heat shock protein , disease , neurodegeneration , hsp70 , protein aggregation , chemical chaperone , drug discovery , chemistry , neuroscience , computational biology , biology , microbiology and biotechnology , biochemistry , medicine , unfolded protein response , gene , pathology
Neurodegenerative disorders, such as Alzheimer's and Huntington's diseases, are associated with the accumulation of misfolded polypeptides. These misfolded proteins have a tendency to self‐associate and these oligomers are believed to cause the memory/behavioral defects seen in patients. The focus of our group's work is to identify new strategies for blocking the toxicity of these oligomers by chemical manipulation of the cell's protein folding machinery. Specifically, we are pursuing small molecules that promote the function of molecular chaperones, such as heat shock protein 70 (Hsp70). Using high throughput screening of focused chemical libraries, in concert with computational and structural approaches, we have identified a number of potential candidate molecules. Interestingly, these candidates control protein aggregation in cell‐based models of neurodegenerative disease. These chemical tools may help elucidate the molecular mechanisms underlying neurodegenerative disorders.