Modifying the blood-brain barrier by targeting claudin-5: Safety and risks.
blood-brain barrier
claudin
regulatory science
tight junction
Journal
Annals of the New York Academy of Sciences
ISSN: 1749-6632
Titre abrégé: Ann N Y Acad Sci
Pays: United States
ID NLM: 7506858
Informations de publication
Date de publication:
08 2022
08 2022
Historique:
pubmed:
5
5
2022
medline:
1
9
2022
entrez:
4
5
2022
Statut:
ppublish
Résumé
The blood-brain barrier is a major obstacle to the delivery of drugs to the central nervous system. In the blood-brain barrier, the spaces between adjacent brain microvascular endothelial cells are sealed by multiprotein complexes known as tight junctions. Among the many components of the tight junction, claudin-5 has received the most attention as a target for loosening the tight-junction seal and allowing drugs to be delivered to the brain. In mice, transient knockdown of claudin-5 and the use of claudin-5 binders have been shown to enhance the permeation of small molecules from the blood into the brain without apparent adverse effects. However, sustained knockdown of claudin-5 in mice is lethal within 40 days, and administration of an anti-claudin-5 antibody induced convulsions in a nonhuman primate. Here, we review the safety concerns of claudin-5-targeted technologies with respect to their clinical application.
Substances chimiques
Claudin-5
0
Types de publication
Journal Article
Review
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
62-69Informations de copyright
© 2022 New York Academy of Sciences.
Références
Rubin, L. L., & Staddon, J. M. (1999). The cell biology of the blood-brain barrier. Annual Review of Neuroscience, 22, 11-28.
Cardoso, F. L., Brites, D., & Brito, M. A. (2010). Looking at the blood brain barrier: Molecular anatomy and possible investigation approaches. Brain Research Reviews, 64, 328-363.
Abbott, N. J., Patabendige, A. A., Dolman, D. E., Yusof, S. R., & Begley, D. J. (2010). Structure and function of the blood-brain barrier. Neurobiology of Disease, 37, 13-25.
Wolburg, H., Noell, S., Mack, A., Wolburg-Buchholz, K., & Fallier-Becker, P. (2009). Brain endothelial cells and the glio-vascular complex. Cell and Tissue Research, 335, 75-96.
Tsukita, S., Furuse, M., & Itoh, M. (2001). Multifunctional strands in tight junctions. Nature Reviews Molecular Cell Biology, 2, 285-293.
Paris, L., Tonutti, L., Vannini, C., & Bazzoni, G. (2008). Structural organization of the tight junctions. Biochimica et Biophysica Acta, 1778, 646-659.
Nitta, T., Hata, M., Gotoh, S., Seo, Y., Sasaki, H., Hashimoto, N., Furuse, M., & Tsukita, S. (2003). Size-selective loosening of the blood-brain barrier in claudin-5-deficient mice. Journal of Cell Biology, 161, 653-660.
Greene, C., Hanley, N., & Campbell, M. (2019). Claudin-5: Gatekeeper of neurological function. Fluids Barriers CNS, 16, 3.
Campbell, M., Kiang, A. S., Kenna, P. F., Kenna, P. F., Kerskens, C., Blau, C., O'Dwyer, L., Tivnan, A., Kelly, J. A., Brankin, B., Farrar, G.-J., & Humphries, P. (2008). RNAi-mediated reversible opening of the blood-brain barrier. Journal of Gene Medicine, 10, 930-947.
Protze, J., Eichner, M., Piontek, A., Dinter, S., Rossa, J., Blecharz, K Gż, Vajkoczy, P., Piontek, J., & Krause, G. (2015). Directed structural modification of Clostridium perfringens enterotoxin to enhance binding to claudin-5. Cellular and Molecular Life Sciences, 72, 1417-1432.
Liao, Z., Yang, Z., Piontek, A., Eichner, M., Krause, G., Li, L., Piontek, J., & Zhang, J. (2016). Specific binding of a mutated fragment of Clostridium perfringens enterotoxin to endothelial claudin-5 and its modulation of cerebral vascular permeability. Neuroscience, 327, 53-63.
Dithmer, S., Staat, C., Muller, C., Ku, M.-C., Pohlmann, A., Niendorf, T., Gehne, N., Fallier-Becker, P., Kittel, Á., Walter, F. R., Veszelka, S., Deli, M. A., Blasig, R., Haseloff, R. F., Blasig, I. E., & Winkler, L. (2017). Claudin peptidomimetics modulate tissue barriers for enhanced drug delivery. Annals of the New York Academy of Sciences, 1397, 169-184.
Breitkreuz-Korff, O., Tscheik, C., Del Vecchio, G., Dithmera, S., Walther, W., Orthmann, A., Wolburg, H., Haseloff, R F., Schrödere, L., Ingolf, E. B, & Winkler, L. (2021). M01 as a novel drug enhancer for specifically targeting the blood-brain barrier. Journal of Controlled Release, 338, 137-148.
Hashimoto, Y., Shirakura, K., Okada, Y., Takeda, H., Endo, K., Tamura, M., Watari, A., Sadamura, Y., Sawasaki, T., Doi, T., Yagi, K., & Kondoh, M. (2017). Claudin-5-binders enhance permeation of solutes across the blood-brain barrier in a mammalian model. Journal of Pharmacology and Experimental Therapeutics, 363, 275-283.
Hashimoto, Y., Zhou, W., Hamauchi, K., Shirakura, K., Doi, T., Yagi, K., Sawasaki, T., Okada, Y., Kondoh, M., & Takeda, H. (2018). Engineered membrane protein antigens successfully induce antibodies against extracellular regions of claudin-5. Science Reports, 8, 8383.
Ikenouchi, J., Furuse, M., Furuse, K., Sasaki, H., Tsukita, S., & Tsukita, S. (2005). Tricellulin constitutes a novel barrier at tricellular contacts of epithelial cells. Journal of Cell Biology, 171, 939-945.
Furuse, M., Izumi, Y., Oda, Y., Higashi, T., & Iwamoto, N. (2014). Molecular organization of tricellular tight junctions. Tissue Barriers, 2, e28960.
Masuda, S., Oda, Y., Sasaki, H., Ikenouchi, J., Higashi, T., Akashi, M., Nishi, E., & Furuse, M. (2011). LSR defines cell corners for tricellular tight junction formation in epithelial cells. Journal of Cell Science, 124, 548-555.
Higashi, T., Tokuda, S., Kitajiri, S., Masuda, S., Nakamura, H., Oda, Y., & Furuse, M. (2013). Analysis of the “angulin” proteins LSR, ILDR1 and ILDR2-tricellulin recruitment, epithelial barrier function and implication in deafness pathogenesis. Journal of Cell Science, 126, 966-977.
Daneman, R., Zhou, L., Agalliu, D., Cahoy, J. D., Kaushal, A., & Barres, B. A. (2010). The mouse blood-brain barrier transcriptome: A new resource for understanding the development and function of brain endothelial cells. PLoS One, 5, e13741.
Krug, S. M., Hayaishi, T., Iguchi, D., Watari, A., Takahashi, A., Fromm, M., Nagahama, M., Takeda, H., Okada, Y., Sawasaki, T., Doi, T., Yagi, K., & Kondoh, M. (2017). Angubindin-1, a novel paracellular absorption enhancer acting at the tricellular tight junction. Journal of Controlled Release, 260, 1-11.
Zeniya, S., Kuwahara, H., Daizo, K., Watari, A., Kondoh, M., Yoshida-Tanaka, K., Kaburagi, H., Asada, K., Nagata, T., Nagahama, M., Yagi, K., & Yokota, T. (2018). Angubindin-1 opens the blood-brain barrier in vivo for delivery of antisense oligonucleotide to the central nervous system. Journal of Controlled Release, 283, 126-134.
Mesli, S., Javorschi, S., Bérard, A. M., Landry, M., Priddle, H., Kivlichan, D., Smith, A. J. H., Yen, F. T., Bihain, B. E., & Darmon, M. (2004). Distribution of the lipolysis stimulated receptor in adult and embryonic murine tissues and lethality of LSR-/- embryos at 12.5 to 14.5 days of gestation. European Journal of Biochemistry, 271, 3103-3114.
Berndt, P., Winkler, L., Cording, J., Breitkreuz-Korff, O., Rex, A., Dithmer, S., Rausch, V., Blasig, R., Richter, M., Sporbert, A., Wolburg, H., Blasig, I. E., & Haseloff, R. F. (2019). Tight junction proteins at the blood-brain barrier: Far more than claudin-5. Cellular and Molecular Life Sciences, 76, 1987-2002.
Suzuki, H., Nishizawa, T., Tani, K., Yamazaki, Y., Tamura, A., Ishitani, R., Dohmae, N., Tsukita, S., Nureki, O., & Fujiyoshi, Y. (2014). Crystal structure of a claudin provides insight into the architecture of tight junctions. Science, 344, 304-307.
Suzuki, H., Tani, K., & Fujiyoshi, Y. (2017). Crystal structures of claudins: Insights into their intermolecular interactions. Annals of the New York Academy of Sciences, 1397, 25-34.
Wen, H., Watry, D. D., Marcondes, M. C. G., & Fox, H. S. (2004). Selective decrease in paracellular conductance of tight junctions: Role of the first extracellular domain of claudin-5. Molecular and Cellular Biology, 24, 8408-8417.
Gunzel, D., & Yu, A. S. (2013). Claudins and the modulation of tight junction permeability Physiological Reviews, 93, 525-569.
Piontek, J., Krug, S. M., Protze, J., Krause, G., & Fromm, M. (2020). Molecular architecture and assembly of the tight junction backbone. Biochimica et Biophysica Acta, 1862, 183279.
Piehl, C., Piontek, J., Cording, J., Wolburg, H., & Blasig, I. E. (2010). Participation of the second extracellular loop of claudin-5 in paracellular tightening against ions, small and large molecules. Cellular and Molecular Life Sciences, 67, 2131-2140.
Sonoda, N., Furuse, M., Sasaki, H., Yonemura, S., Katahira, J., Horiguchi, Y., & Tsukita, S. (1999). Clostridium perfringens enterotoxin fragment removes specific claudins from tight junction strands: Evidence for direct involvement of claudins in tight junction barrier. Journal of Cell Biology, 147, 195-204.
Fujita, K., Katahira, J., Horiguchi, Y., Sonoda, N., Furuse, M., & Tsukita, S. (2000). Clostridium perfringens enterotoxin binds to the second extracellular loop of claudin-3, a tight junction integral membrane protein. FEBS Letters, 476, 258-261.
Kimura, J., Abe, H., Kamitani, S., Toshima, H., Fukui, A., Miyake, M., Kamata, Y., Sugita-Konishi, Y., Yamamoto, S., & Horiguchi, Y. (2010). Clostridium perfringens enterotoxin interacts with claudins via electrostatic attraction. Journal of Biological Chemistry, 285, 401-408.
Winkler, L., Gehring, C., Wenzel, A., Müller, S. L., Piehl, C., Krause, G., Blasig, I. E., & Piontek, J. (2009). Molecular determinants of the interaction between Clostridium perfringens enterotoxin fragments and claudin-3. Journal of Biological Chemistry, 284, 18863-18872.
Mrsny, R. J., Brown, G. T., Gerner-Simidt, K., Buret, A. G., Meddings, J. B., Quan, C., Koval, M., & Nusrat, A. (2008). A key claudin extracellular loop domain is critical for epithelial barrier integrity. American Journal of Pathology, 172, 905-915.
Zwanziger, D., Hackel, D., Staat, C., Böcker, A., Brack, A., Beyermann, M., Rittner, H., & Blasig, I. E. (2012). A peptidomimetic tight junction modulator to improve regional analgesia. Molecular Pharmaceutics, 9, 1785-1794.
Bullock, R. (1995). Mannitol and other diuretics in severe neurotrauma. New Horizons (Baltimore, Md.), 3, 448-452.
Campbell, M., Hanrahan1, F., Gobbo, O. L., Kelly, M E., Kiang, A.-S., Humphries, M. M., Nguyen, A. T.H., Ozaki, E., Keaney, J., Blau, C. W., Kerskens, C. M., Cahalan, S. D., Callanan, J. J., Wallace, E., Grant, G. A., Doherty, C. P., & Humphries, P. (2012). Targeted suppression of claudin-5 decreases cerebral oedema and improves cognitive outcome following traumatic brain injury. Nature Communication, 3, 849.
Greene, C., Kealy, J., Humphries, M. M., Gong, Y., Hou, J., Hudson, N., Cassidy, L. M., Martiniano, R., Shashi, V., Hooper, S. R., Grant, G. A., Kenna, P. F., Norris, K., Callaghan, C. K., dN Islam, M., O'Mara, S. M., Najda, Z., Campbell, S. G., Pachter, J. S., Thomas, J., Williams, N. M., Humphries, P., Murphy, K. C., & Campbell, M. (2018). Dose-dependent expression of claudin-5 is a modifying factor in schizophrenia. Molecular Psychiatry, 23, 2156-2166.
Song, H. W., Foreman, K. L., Gastfriend, B. D., Kuo, J. S., Palecek, S. P., & Shusta, E. V. (2020). Transcriptomic comparison of human and mouse brain microvessels. Science Reports, 10, 12358.
Tachibana, K., Hashimoto, Y., Shirakura, K., Okada, Y., Hirayama, R., Iwashita, Y., Nishino, I., Ago, Y., Takeda, H., Kuniyasu, H., & Kondoh, M. (2021). Safety and efficacy of an anti-claudin-5 monoclonal antibody to increase blood-brain barrier permeability for drug delivery to the brain in a non-human primate. Journal of Controlled Release, 336, 105-111.
Morita, K., Furuse, M., Fujimoto, K., & Tsukita, S. (1999). Claudin multigene family encoding four-transmembrane domain protein components of tight junction strands. Proceedings of the National Academy of Sciences of the United States of America, 96, 511-516.
Omidinia, E., Mazar, F. M., Shahamati, P., Kianmehr, A., & Mohammadi, H. S. (2014). Polymorphism of the CLDN5 gene and schizophrenia in an Iranian population. Iranian Journal of Public Health, 43, 79-83.
Wu, N., Zhang, X., Jin, S., Liu, S., Ju, G., Wang, Z., Liu, L., Ye, L., & Wei, J. (2010). A weak association of the CLDN5 locus with schizophrenia in Chinese case-control samples. Psychiatry Research, 178, 223.
Greene, C., Hanley, N., & Campbell, M. (2020). Blood-brain barrier associated tight junction disruption is a hallmark feature of major psychiatric disorders. Translational Psychiatry, 10, 373.
Usta, A., Kılıç, F., Demirdaş, A., Işık, Ü., Doğuç, D. K., & Bozkurt, M. (2021). Serum zonulin and claudin-5 levels in patients with schizophrenia. European Archives of Psychiatry and Clinical Neuroscience, 271, 767-773.
Menard, C., Pfau, M. L., Hodes, G. E., Kana, V., Wang, V. X., Bouchard, S., Takahashi, A., Flanigan, M. E., Aleyasin, H., LeClair, K. B., Janssen, W. G., Labonté, B., Parise, E. M., Lorsch, Z. S., Golden, S. A., Heshmati, M., Tamminga, C., Turecki, G., Campbell, M., . . . & Russo, S. J. (2017). Social stress induces neurovascular pathology promoting depression. Nature Neuroscience, 20, 1752-1760.
Auriel, E., & Greenberg, S. M. (2012). The pathophysiology and clinical presentation of cerebral amyloid angiopathy. Current Atherosclerosis Reports, 14, 343-350.
Keaney, J., Walsh, D. M., O'Malley, T., Hudson, N., Crosbie, D. E., Loftus, T., Sheehan, F., McDaid, J., Humphries, M. M., Callanan, J. J., Brett, F. M., Farrell, M. A., Humphries, P., & Campbell, M. (2015). Autoregulated paracellular clearance of amyloid-β across the blood-brain barrier. Science Advances, 1, e1500472.
Drouin-Ouellet, J., Sawiak, S. J., & Cisbani, G. (2015). Cerebrovascular and blood-brain barrier impairments in Huntington's disease: Potential implications for its pathophysiology. Annals of Neurology, 78, 160-177.
Carpentier, A., Canney, M., Vignot, A., Reina, V., Beccaria, K., Horodyckid, C., Karachi, C., Leclercq, D., Lafon, C., Chapelon, J.-Y., Capelle, L., Cornu, P., Sanson, M., Hoang-Xuan, K., Delattre, J.-Y., & Idbaih, A. (2016). Clinical trial of blood-brain barrier disruption by pulsed ultrasound. Science Translational Medicine, 8, 343re2.
Neuwelt, A., Frenkel, E. P., Diehl, J., Vu, L. H., Rapoport, S., & Hill, S. (1980). Reversible osmotic blood-brain barrier disruption in humans: Implications for the chemotherapy of malignant brain tumors. Neurosurgery, 7, 44-52.
Helmy, A., Vizcaychipi, M., & Gupta, A. K. (2007). Traumatic brain injury: Intensive care management. British Journal of Anaesthesia, 99, 32-42.
Rapoport, S. I. (2000). Osmotic opening of the blood-brain barrier: Principles, mechanism, and therapeutic applications. Cellular and Molecular Neurobiology, 20, 217-230.
Laksitorini, M., Prasasty, V. D., Kiptoo, P. K., & Siahaan, T. J. (2014). Pathways and progress in improving drug delivery through the intestinal mucosa and blood-brain barriers. Therapeutic Delivery, 5, 1143-1163.
Chen, H., & Konofagou, E. E. (2014). The size of blood-brain barrier opening induced by focused ultrasound is dictated by the acoustic pressure. Journal of Cerebral Blood Flow and Metabolism, 34, 1197-1204.
Furuse, M., & Tsukita, S. (2006). Claudins in occluding junctions of humans and flies. Trends in Cell Biology, 16, 181-188.
Marchi, N., Banhara, M., & Janigro, D. (2016). Blood-brain barrier, bulk flow, and interstitial clearance in epilepsy. Journal of Neuroscience Methods, 260, 118-124.