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Zonulin (haptoglobin 2 precursor)[1] is a protein that increases the permeability of tight junctions between cells of the wall of the digestive tract.[2] It was discovered in 2000 by Alessio Fasano and his team at the University of Maryland School of Medicine. As the mammalian analogue of zonula occludens toxin, secreted by cholera pathogen Vibrio cholerae, zonulin has been implicated in the pathogenesis of coeliac disease and diabetes mellitus type 1.[3] Type 2 diabetic patients have shown increased zonulin.[4]
Gliadin (a glycoprotein present in gluten) activates zonulin signaling irrespective of the genetic expression of autoimmunity, leading to increased intestinal permeability of macromolecules.[3][5]
Zonula occludens toxin is being studied as an adjuvant to improve absorption of drugs and vaccines.[6] In 2014 a zonulin receptor antagonist, larazotide acetate (formerly known as AT-1001), completed a phase 2b clinical trial.[7][8]
^UniProtKB - P00738 (HPT_HUMAN)
^Vanuytsel, T; et al. (Dec 2013). "The role of Haptoglobin and its related protein, Zonulin, in inflammatory bowel disease". Tissue Barriers. 1 (5): e27321. doi:10.4161/tisb.27321. PMC 3943850. PMID 24868498.
^ abFasano, A (Jan 2011). "Zonulin and its regulation of intestinal barrier function: the biological door to inflammation, autoimmunity, and cancer". Physiol. Rev. 91 (1): 151–75. CiteSeerX 10.1.1.653.3967. doi:10.1152/physrev.00003.2008. PMID 21248165.
^Lopetuso LR, Scaldaferri F, Bruno G, Petito V, Franceschi F, Gasbarrini A (2015). "The therapeutic management of gut barrier leaking: the emerging role for mucosal barrier protectors". European Review for Medical and Pharmacological Sciences. 19 (6): 1068–1076. PMID 25855934.
^Visser, Jeroen; Rozing, Jan; Sapone, Anna; Lammers, Karen; Fasano, Alessio (2009-05-01). "Tight Junctions, Intestinal Permeability, and Autoimmunity Celiac Disease and Type 1 Diabetes Paradigms". Annals of the New York Academy of Sciences. 1165: 195–205. doi:10.1111/j.1749-6632.2009.04037.x. ISSN 0077-8923. PMC 2886850. PMID 19538307.
^Lemmer, HJ; Hamman, JH (Jan 2013). "Paracellular drug absorption enhancement through tight junction modulation". Expert Opin Drug Deliv. 10 (1): 103–14. doi:10.1517/17425247.2013.745509. PMID 23163247.
^"Alba Therapeutics announces positive results of phase IIb trial in celiac disease" (Press release). Alba Therapeutics. February 11, 2014.
^Leffler, DA; Kelly, CP; Green, PH; Fedorak, RN; DiMarino, A; Perrow, W; Rasmussen, H; Wang, C; Bercik, P; Bachir, NM; Murray, JA (June 2015). "Larazotide acetate for persistent symptoms of celiac disease despite a gluten-free diet: a randomized controlled trial". Gastroenterology. 148 (7): 1311-9.e6. doi:10.1053/j.gastro.2015.02.008. PMC 4446229. PMID 25683116.
Zonulin (haptoglobin 2 precursor) is a protein that increases the permeability of tight junctions between cells of the wall of the digestive tract. It...
myeloid differentiation factor 88 (MYD88) and the release of zonulin into the lumen. Zonulin then binds to epidermal growth factor receptor (EGFR) and protease-activated...
intestinal epithelium, which respond to zonulin. Gliadin (a glycoprotein present in wheat) activates zonulin signaling in all people who eat gluten, irrespective...
path eventually led him and his team to the "serendipitous" discovery of zonulin in 2000, a protein responsible for regulating intestinal tight-junctions...
Alternative treatments under investigation include the inhibition of zonulin, an endogenous signalling protein linked to increased permeability of the...
journal}}: CS1 maint: multiple names: authors list (link) Fasano A (Jan 2011). "Zonulin and its regulation of intestinal barrier function: the biological door...
Cite journal requires |journal= (help) Fasano, Alessio (1 January 2011). "Zonulin and Its Regulation of Intestinal Barrier Function: The Biological Door...
subgroups of people with autism showed the presence of high plasma levels of zonulin, a protein that regulates permeability opening the "pores" of the intestinal...
(July 2008). "Gliadin induces an increase in intestinal permeability and zonulin release by binding to the chemokine receptor CXCR3". Gastroenterology....
involved in increased risk for type 1 diabetes as zonulin production is also a factor. This triggering of zonulin ultimately results in the degradation of tight...