Zonulin (haptoglobin 2 precursor) is a

protein Proteins are large biomolecules and macromolecules that comprise one or more long chains of amino acid residues. Proteins perform a vast array of functions within organisms, including catalysing metabolic reactions, DNA replication, respon ...

that increases the permeability of

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein junctional complexes whose canonical function is to prevent leakage of solutes and water and seals between the epith ...

s between

cells Cell most often refers to: * Cell (biology), the functional basic unit of life Cell may also refer to: Locations * Monastic cell, a small room, hut, or cave in which a religious recluse lives, alternatively the small precursor of a monastery w ...

of the wall of the

digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the digestive system that leads from the mouth to the anus. The GI tract contains all the major organs of the digestive system, in humans an ...

. It was discovered in 2000 by

Alessio Fasano Alessio Fasano is an Italian-born medical doctor, pediatric gastroenterologist and researcher. He currently holds many roles, including professor of pediatrics at Harvard Medical School and professor of nutrition at Harvard T.H. Chan School of ...

and his team at the

University of Maryland School of Medicine The University of Maryland School of Medicine (abbreviated UMSOM), located in Baltimore City, Maryland, U.S., is the medical school of the University of Maryland, Baltimore and is affiliated with the University of Maryland Medical Center and Med ...

. As the mammalian analogue of zonula occludens toxin, secreted by cholera pathogen ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative, facultative anaerobe and comma-shaped bacteria. The bacteria naturally live in brackish or saltwater where they attach themselves easily to the chitin-containing shells of crabs, shrimps, and ot ...

'', zonulin has been implicated in the pathogenesis of

coeliac disease Coeliac disease (British English) or celiac disease (American English) is a long-term autoimmune disorder, primarily affecting the small intestine, where individuals develop intolerance to gluten, present in foods such as wheat, rye and barl ...

and

diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that originates when cells that make insulin (beta cells) are destroyed by the immune system. Insulin is a hormone required for the cells to use blood sugar f ...

. Type 2 diabetic patients have shown increased zonulin.

Gliadin Gliadin (a type of prolamin) is a class of proteins present in wheat and several other cereals within the grass genus ''Triticum''. Gliadins, which are a component of gluten, are essential for giving bread the ability to rise properly during bak ...

(a glycoprotein present in

gluten Gluten is a structural protein naturally found in certain cereal grains. Although "gluten" often only refers to wheat proteins, in medical literature it refers to the combination of prolamin and glutelin proteins naturally occurring in all gra ...

) activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased

intestinal permeability Intestinal permeability is a term describing the control of material passing from inside the gastrointestinal tract through the cells lining the gut wall, into the rest of the body. The intestine normally exhibits some permeability, which allows ...

of macromolecules. Zonula occludens toxin is being studied as an adjuvant to improve absorption of drugs and vaccines. In 2014 a zonulin receptor antagonist,

larazotide acetate Larazotide (INN; also known as AT-1001; formulated as the salt with acetic acid, larazotide acetate) is a synthetic eight amino acid peptide that functions as a tight junction regulator and reverses leaky junctions to their normally closed state. ...

(formerly known as AT-1001), completed a phase 2b clinical trial.{{cite journal , last1=Leffler , first1=DA , last2=Kelly , first2=CP , last3=Green , first3=PH , last4=Fedorak , first4=RN , last5=DiMarino , first5=A , last6=Perrow , first6=W , last7=Rasmussen , first7=H , last8=Wang , first8=C , last9=Bercik , first9=P , last10=Bachir , first10=NM , last11=Murray , first11=JA , title=Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial. , journal=Gastroenterology , date=June 2015 , volume=148 , issue=7 , pages=1311-9.e6 , doi=10.1053/j.gastro.2015.02.008 , pmid=25683116, pmc=4446229

References

Digestive system

See also

References