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HOME > PAST ISSUE > July-August 2005 > Article Detail

FEATURE ARTICLE

A New Understanding of Protein Mutation Unfolds

Long believed to be nonfunctional, mutant proteins that cause disease can often behave normally when refolded with the help of a pharmacological template

P. Michael Conn and Jo Ann Janovick

Figure 2. DNA in the nucleus contains information...Click to Enlarge Image

Most diseases with a genetic basis involve a mutation in some gene that affects how much of its protein is made or how well that protein works. However, a growing body of research indicates that this scenario may not be universally true. Conn and Janovick explain that many diseases, including cystic fibrosis, Alzheimer's and diabetes, are products of improperly folded—but potentially functional—proteins. When the authors added a template for correct folding (which they call a pharmacoperone) to a cell with such a "mutant" protein, the cellular defect was fixed. This remedy suggests that the rescue of a person's own misfolded proteins may be an alternative to the broader physiological tinkering (and attendant side effects) caused by most of the current drugs used to treat these diseases.


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