A pharmacological chaperone or pharmacoperone is a drug that acts as a protein chaperone. That is, it contains small

molecule A molecule is a group of two or more atoms that are held together by Force, attractive forces known as chemical bonds; depending on context, the term may or may not include ions that satisfy this criterion. In quantum physics, organic chemi ...

s that enter cells and serve as a molecular scaffolding in order to cause otherwise- misfolded mutant

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residue (biochemistry), residues. Proteins perform a vast array of functions within organisms, including Enzyme catalysis, catalysing metab ...

s to fold and route correctly within the cell. Mutation of proteins often causes molecular misfolding, which results in protein misrouting within the cell. Accordingly, mutant molecules may retain proper function but end up in parts of the cell where the function is inappropriate, or even deleterious, to cell function. Misfolded proteins are usually recognized by the quality-control system of the cell and retained (and often destroyed or recycled) in the

endoplasmic reticulum The endoplasmic reticulum (ER) is a part of a transportation system of the eukaryote, eukaryotic cell, and has many other important functions such as protein folding. The word endoplasmic means "within the cytoplasm", and reticulum is Latin for ...

. Pharmacoperones correct the folding of misfolded proteins, allowing them to pass through the cell's quality-control system and become correctly routed. Since mutations often cause disease by causing misfolding and misrouting, pharmacoperones are potentially therapeutic agents, since they are able to correct this defect. Diseases that may be susceptible to such treatments include

diabetes Diabetes mellitus, commonly known as diabetes, is a group of common endocrine diseases characterized by sustained high blood sugar levels. Diabetes is due to either the pancreas not producing enough of the hormone insulin, or the cells of th ...

, inherited

cataract A cataract is a cloudy area in the lens (anatomy), lens of the eye that leads to a visual impairment, decrease in vision of the eye. Cataracts often develop slowly and can affect one or both eyes. Symptoms may include faded colours, blurry or ...

s and

cystic fibrosis Cystic fibrosis (CF) is a genetic disorder inherited in an autosomal recessive manner that impairs the normal clearance of Sputum, mucus from the lungs, which facilitates the colonization and infection of the lungs by bacteria, notably ''Staphy ...

Examples

* Migalastat is a pharmacological chaperone for the treatment of Fabry disease. *

Tafamidis Tafamidis, sold under the brand names Vyndaqel and Vyndamax, is a medication used to delay disease progression in adults with certain forms of transthyretin amyloidosis. It can be used to treat both hereditary forms, familial amyloid cardiomyo ...

is a pharmacological chaperone for the treatment of

transthyretin Transthyretin (TTR or TBPA) is a transport protein in the plasma and cerebrospinal fluid that transports the thyroid hormone thyroxine (T4) and retinol to the liver. This is how transthyretin gained its name: ''transports thyroxine and retinol' ...

amyloidosis Amyloidosis is a group of diseases in which abnormal proteins, known as amyloid fibrils, build up in tissue. There are several non-specific and vague signs and symptoms associated with amyloidosis. These include fatigue, peripheral edema, weigh ...

(ATTR). * Lumacaftor and tezacaftor are pharmacological chaperones used in

that target the CFTR protein. * In 2013, mice with a disease that makes the males unable to father offspring were cured by use of pharmacoperones.

References

Sources

*Conn, P.M. and Janovick, J.A., A New Understanding of Protein Mutation Unfolds, American Scientist 93:314-321, 2005. {{DEFAULTSORT:Pharmacological Chaperone Dosage forms Protein folding Therapy Molecular chaperones

Examples

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References

Sources