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Restoring Protein Homeostasis to Ameliorate Human Disease
Author(s) -
Kelly Jeffery W
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.536.1
Subject(s) - proteostasis , loss function , biology , gain of function , protein aggregation , disease , function (biology) , regulator , unfolded protein response , neuroscience , bioinformatics , microbiology and biotechnology , medicine , endoplasmic reticulum , mutation , phenotype , genetics , gene
The misfolding and/or misassembly of a given intracellular protein leads to gain of toxic function diseases, including Huntington's and Parkinson's, and loss of function diseases including cystic fibrosis and the lysosomal storage diseases. Intra‐ and extracellular protein misfolding and/or misassembly also appears to cause age onset neurodegenerative diseases known as the amyloidoses, including Alzheimer's and the numerous familial disorders such as the transthyretin amyloidoses. The talk will start with an overview of the mechanistic insight that we and others have acquired from studying loss and gain of function diseases of protein homeostasis. I will then focus on the restoration of protein homeostasis in diseases where age onset loss of control of proteostasis has occurred, using a new therapeutic strategy involving small molecules and biologicals that influence the biology of proteostasis. In other words, we aim to reprogram evolved and innate biological networks to repair damaged proteins associated with loss‐ or gain‐of‐toxic function diseases. Several examples of the power of proteostasis regulators will be discussed along with their mechanisms of action. This strategy is highly appealing as one proteostasis regulator can be used to ameliorate several diseases of similar origin.