Xylosyltransferase 1 is anenzyme that in humans is encoded by theXYLT1gene.[5][6]
Xylosyltransferase (XT; EC 2.4.2.26)catalyzes the transfer of UDP-xylose toserine residues within XT recognition sequences of target proteins. Addition of thisxylose to the core protein is required for the biosynthesis of theglycosaminoglycan chains characteristic ofproteoglycans.[supplied by OMIM][6]
In 2012 Baratela-Scott syndrome was identified in humans.[7] A GGC repeat expansion, andmethylation ofexon 1 of XYLT1 is a common pathogenic variant in Baratela-Scott syndrome.[8]
Patients with Bartarlla-Scott syndrome exhibitabnormaldevelopment of theskeleton, characteristic facial features, and cognitive developmental delay. Skeletal problems include knee cap in thewrong position, shortlong bones with mild changes to the narrow portion,shortpalm bones with stub thumbs, shortthigh necks,shallow hip sockets, andmalformations of the spine. Characteristic facial features include a flattened midface with a broadnasal bridge,cleft palate, andunibrow. The syndrome also cause pre-school onset of a cognitive developmental delay, with a shortened attention span. Some of the cognitive delay is masked by a warm and engaging personality.
Neurons use the presence of extracellular matrix molecules as clues whether to promote or suppress extension of axons. Chondroitin sulfate proteoglycans suppress the extension of axons over the glial scar, a barrier which develops after lesioning the spinal cord. Proteoglycans consist of one relatively small protein core and attached large glycosaminoglycan side chains. To block the very formation of these side chains xylosyltransferase (XYLT1) which attaches xylose to a serine of the protein core as initiation for glycosaminoglycan chain extension, was targeted by a class of designed DNA molecules. These molecules are called DNA-enzymes which were designed to specifically cleave XYLT1 mRNA within cells. DNA-enzymes are readily taken up by mammalian cells, but are more stable and require much lower concentrations then siRNA. XTYL1 DNA-enzyme in co-cultures of neurons with neurocan secreting cells displayed a marked increase of axon outgrowth. Rats with defined spinal cord lesions, i.a. the clinically relevant contusion injury, treated with XTYL1 DNA-enzyme administered by micro-infusion pumps or systemically achieved improvements in the horizontal ladder task, enhanced axonal plasticity, growth of the corticospinal tract, no effect on neuropathic pain when using mechanical and thermal allodynia tests and no toxicological or pathological side effects compared to control animals.{{Oudega M, Chao OY, Avison DL, Bronson RT, Buchser WJ, Hurtado A, Grimpe B. (2012) Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord injury Exp Neurol. Sep;237(1):170-9. doi: 10.1016/j.expneurol.2012.06.006. PMID: 22721770}}
^"Human PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^"Mouse PubMed Reference:".National Center for Biotechnology Information, U.S. National Library of Medicine.
^Götting C, Kuhn J, Zahn R, Brinkmann T, Kleesiek K (December 2000). "Molecular cloning and expression of human UDP-d-Xylose:proteoglycan core protein beta-d-xylosyltransferase and its first isoform XT-II".Journal of Molecular Biology.304 (4):517–528.doi:10.1006/jmbi.2000.4261.PMID11099377.
Götting C, Hendig D, Adam A, Schön S, Schulz V, Szliska C, et al. (December 2005). "Elevated xylosyltransferase I activities in pseudoxanthoma elasticum (PXE) patients as a marker of stimulated proteoglycan biosynthesis".Journal of Molecular Medicine.83 (12):984–992.doi:10.1007/s00109-005-0693-x.PMID16133423.S2CID9907867.
Grimpe B, Pressman Y, Lupa MD, Horn KP, Bunge MB, Silver J (January 2005). "The role of proteoglycans in Schwann cell/astrocyte interactions and in regeneration failure at PNS/CNS interfaces".Molecular and Cellular Neurosciences.28 (1):18–29.doi:10.1016/j.mcn.2004.06.010.PMID15607938.S2CID38001196.
Hurtado A, Podinin H, Oudega M, Grimpe B (October 2008). "Deoxyribozyme-mediated knockdown of xylosyltransferase-1 mRNA promotes axon growth in the adult rat spinal cord".Brain.131 (Pt 10):2596–2605.doi:10.1093/brain/awn206.PMID18765417.
Koenig B, Pape D, Chao O, Bauer J, Grimpe B (February 2016). "Long term study of deoxyribozyme administration to XT-1 mRNA promotes corticospinal tract regeneration and improves behavioral outcome after spinal cord injury".Experimental Neurology.276:51–58.doi:10.1016/j.expneurol.2015.09.015.PMID26428904.S2CID10575072.
Oudega M, Chao OY, Avison DL, Bronson RT, Buchser WJ, Hurtado A, et al. (September 2012). "Systemic administration of a deoxyribozyme to xylosyltransferase-1 mRNA promotes recovery after a spinal cord contusion injury".Experimental Neurology.237 (1):170–179.doi:10.1016/j.expneurol.2012.06.006.PMID22721770.S2CID34942901.
