title: Use of polysialic acid in repair of the central nervous system.
abstract: Polysialic acid (PSA), a large cell-surface carbohydrate that regulates cell interactions, is used during vertebrate development to promote precursor cell migration and axon path-finding. The induction of PSA expression in damaged adult CNS tissues could help them to rebuild by creating conditions permissive for architectural remodeling. This possibility has been explored in two contexts, the regeneration of axons and the recruitment of endogenous neural precursors to a lesion. Glial scars that form at CNS injury sites block axon regeneration. It has been found that transfection of scar astrocytes by a viral vector encoding polysialyltransferase leads to sustained expression of high levels of PSA. With this treatment, a substantial portion of severed corticospinal tract axon processes were able to grow through a spinal injury site. In the studies of precursor cell migration to a cortical lesion, it was found that induced PSA expression in a path extending from the subventricular zone to a lesion near the cortical surface increased recruitment of BrdU/nestin-positive cells along the path and into the injury site. These displaced precursors were able to differentiate in a regionally appropriate manner. These findings suggest that induced PSA expression can be used as a strategy for promoting tissue repair involving both replacement of cells and rebuilding of neural connections.
authors.affiliation: Laboratory of Cellular and Developmental Neuroscience, Department of Cell Biology, Memorial Sloan-Kettering Cancer Center, 1275 York Avenue, New York, NY 10021, USA. a-el-maarouf@ski.mskcc.org
authors.forename: Abderrahman
authors.initials: A
authors.lastname: El Maarouf
authors.forename: Athanasios K
authors.initials: AK
authors.lastname: Petridis
authors.forename: Urs
authors.initials: U
authors.lastname: Rutishauser
mesh_terms: D000818:Animals; D001253:Astrocytes / Q000378:metabolism / Q000473:pathology; D001369:Axons / Q000378:metabolism / Q000473:pathology; D001930:Brain Injuries / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D002465:Cell Movement; D002490:Central Nervous System / Q000187:drug effects* / Q000293:injuries* / Q000378:metabolism; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D009416:Nerve Regeneration / Q000187:drug effects; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D012794:Sialic Acids / Q000096:biosynthesis* / Q000627:therapeutic use*; D012799:Sialyltransferases / Q000235:genetics / Q000378:metabolism; D013234:Stem Cells / Q000378:metabolism / Q000473:pathology; D014162:Transfection
chemical_list: D011994:Recombinant Proteins; D012794:Sialic Acids; C021319:polysialic acid; C046778:CMP-N-acetylneuraminate-poly-alpha-2,8-sialosyl sialyltransferase; D012799:Sialyltransferases