<?xml version="1.1" encoding="utf-8"?>
<article xsi:noNamespaceSchemaLocation="http://jats.nlm.nih.gov/publishing/1.1/xsd/JATS-journalpublishing1-mathml3.xsd" dtd-version="1.1" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance"><front><journal-meta><journal-id journal-id-type="publisher-id">MRP</journal-id><journal-title-group><journal-title>Medical Research and Practice</journal-title></journal-title-group><issn>2993-9690</issn><eissn>2993-9704</eissn><publisher><publisher-name>Art and Design</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="doi">10.61369/MRP.11871</article-id><article-categories><subj-group subj-group-type="heading"><subject>Article</subject></subj-group></article-categories><title>解整合素-金属蛋白酶22的生物学作用研究进展</title><url>https://artdesignp.com/journal/MRP/2/12/10.61369/MRP.11871</url><author>仲达,郁丽娜</author><pub-date pub-type="publication-year"><year>2024</year></pub-date><volume>2</volume><issue>12</issue><history><date date-type="pub"><published-time>2024-12-20</published-time></date></history><abstract>解整合素-金属蛋白酶22（ADAM22）是ADAMs蛋白家族的重要成员，其在神经系统、心血管系统和肿瘤等多种生理和病理过程中发挥关键作用。在神经系统中，ADAM22在突触成熟、突触传递和髓鞘形成过程中发挥重要作用，并与癫痫等神经疾病密切相关。此外，ADAM22与LGI4的相互作用在周围神经髓鞘形成中不可或缺。在心血管系统中，ADAM22在血管损伤后的内膜新生和心肌肥厚等病理过程中表现出显著的调控作用。在肿瘤领域，ADAM22在乳腺癌、胃癌等多种肿瘤中高表达，并通过激活整合素信号通路促进肿瘤细胞的增殖和迁移。尽管ADAM22在多种疾病中的作用逐渐被揭示，但其在不同病理过程中的具体分子机制仍需进一步研究。未来针对ADAM22的靶向治疗策略，如基于LGI1的抗肿瘤治疗，可能为相关疾病的治疗提供新的思路。</abstract><keywords>解整合素-金属蛋白酶22,突触,髓鞘,心血管,肿瘤</keywords></article-meta></front><body/><back><ref-list><ref id="B1" content-type="article"><label>1</label><element-citation publication-type="journal"><p>[1]Blobel CP, Wolfsberg TG, Turck CW, Myles DG, Primakoff P, White JM. A potential fusion peptide and an integrin ligand domain in a protein active in sperm-egg fusion.Nature. 1992;356(6366):248-252. doi:10.1038/356248a0.[2]Lichtenthaler SF, Lemberg MK, Fluhrer R. Proteolytic ectodomain shedding of membrane proteins in mammals&amp;mdash;hardware, concepts, and recent developments. The EMBOJournal. 2018;37(15):e99456. doi:10.15252/embj.201899456.[3]Cho C. Testicular and epididymal ADAMs: expression and function during fertilization. Nat Rev Urol. 2012;9(10):550-560. doi:10.1038/nrurol.2012.167.[4]Weber S, Saftig P. Ectodomain shedding and ADAMs in development. Development. 2012;139(20):3693-3709. doi:10.1242/dev.076398.[5]Mullooly M, McGowan PM, Crown J, Duffy MJ. The ADAMs family of proteases as targets for the treatment of cancer. Cancer Biol Ther. 2016;17(8):870-880. doi:10.1080/15384047.2016.1177684.[6]St&amp;ouml;cker W, Grams F, Baumann U, et al. The metzincins--topological and sequential relations between the astacins, adamalysins, serralysins, and matrixins (collagenases)define a superfamily of zinc-peptidases. Protein Sci. 1995;4(5):823-840. doi:10.1002/pro.5560040502.2024.12 | 015[7]Sagane K, Ohya Y, Hasegawa Y, Tanaka I. Metalloproteinase-like, disintegrin-like, cysteine-rich proteins MDC2 and MDC3: novel human cellular disintegrins highly expressed in the brain. Biochemical Journal. 1998;334(1):93-98. doi:10.1042/bj3340093.[8]Sagane K, Hayakawa K, Kai J, et al. Ataxia and peripheral nerve hypomyelination in ADAM22-deficient mice. BMC Neurosci. 2005;6(1):33. doi:10.1186/1471-2202-6-33.[9]Fukata Y, Adesnik H, Iwanaga T, Bredt DS, Nicoll RA, Fukata M. Epilepsy-Related Ligand/Receptor Complex LGI1 and ADAM22 Regulate Synaptic Transmission. Science. 2006;313(5794):1792-1795. doi:10.1126/science.1129947.[10]Lovero KL, Fukata Y, Granger AJ, Fukata M, Nicoll RA. The LGI1&amp;ndash;ADAM22 protein complex directs synapse maturation through regulation of PSD-95 function. Proc Natl Acad Sci USA. 2015;112(30). doi:10.1073/pnas.1511910112.[11]Fukata Y, Lovero KL, Iwanaga T, et al. Disruption of LGI1-linked synaptic complex causes abnormal synaptic transmission and epilepsy. Proc Natl Acad Sci U S A. 2010;107(8):3799-3804. doi:10.1073/pnas.0914537107.[12]Dazzo E, Leonardi E, Belluzzi E, et al. Secretion-Positive LGI1 Mutations Linked to Lateral Temporal Epilepsy Impair Binding to ADAM22 and ADAM23 Receptors. PLoS Genet. 2016;12(10):e1006376. doi:10.1371/journal.pgen.1006376.[13]Yokoi N, Fukata Y, Kase D, et al. Chemical corrector treatment ameliorates increased seizure susceptibility in a mouse model of familial epilepsy. Nat Med. 2015;21(1):19-26. doi:10.1038/nm.3759.[14]Yamagata A, Miyazaki Y, Yokoi N, et al. Structural basis of epilepsy-related ligand&amp;ndash;receptor complex LGI1&amp;ndash;ADAM22. Nat Commun. 2018;9(1):1546. doi:10.1038/s41467-018-03947-w.[15]&amp;Ouml;zkaynak E, Abello G, Jaegle M, et al. Adam22 Is a Major Neuronal Receptor for Lgi4-Mediated Schwann Cell Signaling. J Neurosci. 2010;30(10):3857-3864. doi:10.1523/JNEUROSCI.6287-09.2010.[16]Xue S, Maluenda J, Marguet F, et al. Loss-of-Function Mutations in LGI4, a Secreted Ligand Involved in Schwann Cell Myelination, Are Responsible for Arthrogryposis Multiplex Congenita. The American Journal of Human Genetics. 2017;100(4):659-665. doi:10.1016/j.ajhg.2017.02.006.[17]Horiuchi K, Weskamp G, Lum L, et al. Potential role for ADAM15 in pathological neovascularization in mice. Mol Cell Biol. 2003;23(16):5614-5624. doi:10.1128/MCB.23.16.5614-5624.2003.[18]Hartmann D, de Strooper B, Serneels L, et al. The disintegrin/metalloprotease ADAM 10 is essential for Notch signalling but not for alpha-secretase activity in fibroblasts. Hum Mol Genet. 2002;11(21):2615-2624. doi:10.1093/hmg/11.21.2615.[19]Zhou HM, Weskamp G, Chesneau V, et al. Essential role for ADAM19 in cardiovascular morphogenesis. Mol Cell Biol. 2004;24(1):96-104. doi:10.1128/MCB.24.1.96-104.2004.[20]Kurohara K, Komatsu K, Kurisaki T, et al. Essential roles of Meltrin beta (ADAM19) in heart development. Dev Biol. 2004;267(1):14-28. doi:10.1016/j.ydbio.2003.10.021.[21]Ohtsu H, Dempsey PJ, Eguchi S. ADAMs as mediators of EGF receptor transactivation by G protein-coupled receptors. Am J Physiol Cell Physiol. 2006;291(1):C1-10. doi:10.1152/ajpcell.00620.2005.[22]Zhang SM, Jiang L, Zhao X, et al. A disintegrin and metalloprotease 22 accelerates neointima formation by activating ERK signaling. Atherosclerosis. 2019;283:92-99. doi:10.1016/j.atherosclerosis.2019.02.002.[23]Ren L, Wu C, Yang K, et al. A Disintegrin and Metalloprotease-22 Attenuates Hypertrophic Remodeling in Mice Through Inhibition of the Protein Kinase B Signaling Pathway. J Am Heart Assoc. 2018;7(2):e005696. doi:10.1161/JAHA.117.005696.[24]Bolger JC. ADAM22 as a Prognostic and Therapeutic Drug Target in the Treatment of Endocrine-Resistant Breast Cancer.[25]Charmsaz S, Doherty B, Cocchiglia S, et al. ADAM22/LGI1 complex as a new actionable target for breast cancer brain metastasis. BMC Med. 2020;18(1):349. doi:10.1186/s12916-020-01806-4.[26]McCartan D, Bolger JC, Fagan A, et al. Global characterization of the SRC-1 transcriptome identifies ADAM22 as an ER-independent mediator of endocrine-resistant breast cancer. Cancer Res. 2012;72(1):220-229. doi:10.1158/0008-5472.CAN-11-1976.[27.Xing B, Lei Z, Wang Z, et al. A disintegrin and metalloproteinase 22 activates integrin &amp;beta; 1 through its disintegrin domain to promote the progression of pituitary adenoma. Neuro-Oncology. 2024;26(1):137-152. doi:10.1093/neuonc/noad148.[28]Zhu P, Sang Y, Xu H, et al. ADAM22 plays an important role in cell adhesion and spreading with the assistance of 14-3-3. Biochem Biophys Res Commun. 2005;331(4):938-946. doi:10.1016/j.bbrc.2005.03.229.[29]Murphy G. The ADAMs: signalling scissors in the tumour microenvironment. Nat Rev Cancer. 2008;8(12):929-941. doi:10.1038/nrc2459.[30]Fridman JS, Caulder E, Hansbury M, et al. Selective inhibition of ADAM metalloproteases as a novel approach for modulating ErbB pathways in cancer. Clin Cancer Res. 2007;13(6):1892-1902. doi:10.1158/1078-0432.CCR-06-2116.[31]Kenny PA, Bissell MJ. Targeting TACE-dependent EGFR ligand shedding in breast cancer. J Clin Invest. 2007;117(2):337-345. doi:10.1172/JCI29518.[32]Gabellini N, Masola V. Expression of LGI1 Impairs Proliferation and Survival of HeLa Cells. Int J Cell Biol. 2009;2009:417197. doi:10.1155/2009/417197.[33]RETRACTION:Increased expression of LGI1 gene triggers growth inhibition and apoptosis of neuroblastoma cells. J Cell Physiol. 2024;239(11):e31411. doi:10.1002/jcp.31411.[34]Kunapuli P, Kasyapa CS, Hawthorn L, Cowell JK. LGI1, a putative tumor metastasis suppressor gene, controls in vitro invasiveness and expression of matrix metalloproteinases in glioma cells through the ERK1/2 pathway. J Biol Chem. 2004;279(22):23151-23157. doi:10.1074/jbc.M314192200</p><pub-id pub-id-type="doi"/></element-citation></ref></ref-list></back></article>
