Zonulin

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Alessio Fasano Fasano-200x300.jpg
Alessio Fasano

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]

See also

References

  1. ↑ UniProtKB - P00738 (HPT_HUMAN)
  2. ↑ 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.
  3. 1 2 Fasano, 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.
  4. ↑ 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.
  5. ↑ 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.
  6. ↑ 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.
  7. ↑ "Alba Therapeutics announces positive results of phase IIb trial in celiac disease" (Press release). Alba Therapeutics. February 11, 2014.
  8. ↑ 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.
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