Zonulin (

haptoglobin Haptoglobin (abbreviated as Hp) is the protein that in humans is encoded by the ''HP'' gene. In blood plasma, haptoglobin binds with high affinity to ''free'' hemoglobin released from erythrocytes, and thereby inhibits its deleterious oxidativ ...

2 precursor) is a

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 ...

that increases the permeability of

tight junction Tight junctions, also known as occluding junctions or ''zonulae occludentes'' (singular, ''zonula occludens''), are multiprotein Cell junction, junctional complexes between epithelial cells, sealing and preventing leakage of solutes and water. Th ...

s between

cells Cell most often refers to: * Cell (biology), the functional basic unit of life * Cellphone, a phone connected to a cellular network * Clandestine cell, a penetration-resistant form of a secret or outlawed organization * Electrochemical cell, a d ...

of the wall of the

digestive tract The gastrointestinal tract (GI tract, digestive tract, alimentary canal) is the tract or passageway of the Digestion, digestive system that leads from the mouth to the anus. The tract is the largest of the body's systems, after the cardiovascula ...

. It was discovered in 2000 by Alessio Fasano 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 ...

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

cholera Cholera () is an infection of the small intestine by some Strain (biology), strains of the Bacteria, bacterium ''Vibrio cholerae''. Symptoms may range from none, to mild, to severe. The classic symptom is large amounts of watery diarrhea last ...

pathogen ''

Vibrio cholerae ''Vibrio cholerae'' is a species of Gram-negative bacteria, Gram-negative, Facultative anaerobic organism, facultative anaerobe and Vibrio, comma-shaped bacteria. The bacteria naturally live in Brackish water, brackish or saltwater where they att ...

'', 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. Patients develop intolerance to gluten, which is present in foods such as wheat, rye, spelt ...

and

diabetes mellitus type 1 Type 1 diabetes (T1D), formerly known as juvenile diabetes, is an autoimmune disease that occurs when the body's immune system destroys pancreatic cells (beta cells). In healthy persons, beta cells produce insulin. Insulin is a hormone required ...

. 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 ba ...

(a glycoprotein present in

gluten Gluten is a structural protein naturally found in certain Cereal, cereal grains. The term ''gluten'' usually refers to the elastic network of a wheat grain's proteins, gliadin and glutenin primarily, that forms readily with the addition of water ...

) 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 n ...

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

receptor antagonist A receptor antagonist is a type of receptor ligand or drug that blocks or dampens a biological response by binding to and blocking a receptor rather than activating it like an agonist. Antagonist drugs interfere in the natural operation of rec ...

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 Precursor proteins

See also

References