{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T13:42:26Z","timestamp":1790516546805,"version":"4.1.0"},"reference-count":53,"publisher":"SAGE Publications","issue":"9","license":[{"start":{"date-parts":[[2018,9,1]],"date-time":"2018-09-01T00:00:00Z","timestamp":1535760000000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/journals.sagepub.com\/page\/policies\/text-and-data-mining-license"}],"content-domain":{"domain":["journals.sagepub.com"],"crossmark-restriction":true},"short-container-title":["OMICS: A Journal of Integrative Biology"],"published-print":{"date-parts":[[2018,9]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>\n                    Spinal muscular atrophy (SMA) is one of the most common childhood onset neurodegenerative disorders in global health whereby novel biomarkers and therapeutic targets are sorely needed. SMA is an autosomal recessive genetic disorder resulting in degeneration of \u03b1-motor neurons in the brain stem and spinal cord that leads to mortality in infants worldwide. In majority of the patients, SMA is caused by homozygous deletion of the\n                    <jats:italic toggle=\"yes\">SMN1<\/jats:italic>\n                    gene. The clinical spectrum of the SMA displays, however, large person-to-person variations where the underlying mechanisms are poorly understood. We report in this study transcriptomics insights gleaned from patients with the severe type I (GM03813 and GM09677) and the mild type III. Pathway enrichment and functional analysis showed that especially extracellular matrix (ECM), synapse organization, and ECM receptor interaction pathways were affected. Among the neural ECM components,\n                    <jats:italic toggle=\"yes\">hyaluronan and proteoglycan link protein<\/jats:italic>\n                    (\n                    <jats:italic toggle=\"yes\">HAPLN1<\/jats:italic>\n                    ), which is a key triggering molecule of the perineuronal net (PNN), was significantly downregulated in type I fibroblasts compared to type III. PNN is a specialized form of neural ECM around the neuronal cell bodies and dendrites in the central nervous system. In addition, we evaluated the PNN expression\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    in a model established by\n                    <jats:italic toggle=\"yes\">SMN<\/jats:italic>\n                    silencing in the PC12 rat pheochromocytoma cell line which can be differentiated into neurons with nerve growth factor treatment. In this neuronal\n                    <jats:italic toggle=\"yes\">in vitro<\/jats:italic>\n                    model, we found that HAPLN1 showed a significant 50% decrease. Our results describe the association between PNN elements, especially\n                    <jats:italic toggle=\"yes\">HAPLN1<\/jats:italic>\n                    , and SMA pathophysiology for the first time. These observations collectively inform future translational research on SMA for discovery of novel molecular targets for diagnostics and precision medicine innovation.\n                  <\/jats:p>","DOI":"10.1089\/omi.2018.0106","type":"journal-article","created":{"date-parts":[[2018,8,14]],"date-time":"2018-08-14T14:45:14Z","timestamp":1534257914000},"page":"598-606","update-policy":"https:\/\/doi.org\/10.1177\/sage-journals-update-policy","source":"Crossref","is-referenced-by-count":8,"title":["Do Perineuronal Net Elements Contribute to Pathophysiology of Spinal Muscular Atrophy? In Vitro and Transcriptomics Insights"],"prefix":"10.1177","volume":"22","author":[{"given":"Didem","family":"Dayangac-Erden","sequence":"first","affiliation":[{"name":"Hacettepe University","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bala","family":"Gur-Dedeoglu","sequence":"additional","affiliation":[{"name":"Ankara University","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fatma Nazli","family":"Eskici","sequence":"additional","affiliation":[{"name":"Hacettepe University","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yasemin","family":"Oztemur-Islakoglu","sequence":"additional","affiliation":[{"name":"Ankara University","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sevim","family":"Erdem-Ozdamar","sequence":"additional","affiliation":[{"name":"Hacettepe University","place":["Turkey"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"179","published-online":{"date-parts":[[2018,9,18]]},"reference":[{"key":"e_1_3_4_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nmd.2011.03.009"},{"key":"e_1_3_4_3_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1750-3639.2008.00195.x"},{"key":"e_1_3_4_4_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12031-007-0024-5"},{"key":"e_1_3_4_5_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awq145"},{"key":"e_1_3_4_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2003.12.002"},{"key":"e_1_3_4_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/6.8.1205"},{"key":"e_1_3_4_8_1","doi-asserted-by":"publisher","DOI":"10.1006\/nbdi.1996.0010"},{"key":"e_1_3_4_9_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/5214961"},{"key":"e_1_3_4_10_1","doi-asserted-by":"publisher","DOI":"10.1186\/s11658-018-0073-5"},{"key":"e_1_3_4_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.nimb.2007.02.069"},{"key":"e_1_3_4_12_1","doi-asserted-by":"publisher","DOI":"10.1002\/stem.1812"},{"key":"e_1_3_4_13_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06108.x"},{"key":"e_1_3_4_14_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2012.05.055"},{"key":"e_1_3_4_15_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2010.08.032"},{"key":"e_1_3_4_16_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1440-1789.2008.00888.x"},{"key":"e_1_3_4_17_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0387-7604(02)00103-1"},{"key":"e_1_3_4_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.cellsig.2013.11.027"},{"key":"e_1_3_4_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12565-016-0375-5"},{"key":"e_1_3_4_20_1","doi-asserted-by":"publisher","DOI":"10.1093\/biostatistics\/4.2.249"},{"key":"e_1_3_4_21_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1471-4159.2010.06878.x"},{"key":"e_1_3_4_22_1","doi-asserted-by":"publisher","DOI":"10.1002\/dneu.20974"},{"key":"e_1_3_4_23_1","doi-asserted-by":"publisher","DOI":"10.1016\/0092-8674(95)90460-3"},{"key":"e_1_3_4_24_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0797-265"},{"key":"e_1_3_4_25_1","doi-asserted-by":"publisher","DOI":"10.1002\/jnr.24021"},{"key":"e_1_3_4_26_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btm201"},{"key":"e_1_3_4_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s12974-018-1161-1"},{"key":"e_1_3_4_28_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.96.11.6307"},{"key":"e_1_3_4_29_1","doi-asserted-by":"publisher","DOI":"10.1097\/00125817-200201000-00004"},{"key":"e_1_3_4_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neulet.2008.06.059"},{"key":"e_1_3_4_31_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuint.2012.08.007"},{"key":"e_1_3_4_32_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2012.08268.x"},{"key":"e_1_3_4_33_1","doi-asserted-by":"publisher","DOI":"10.1155\/2016\/1305801"},{"key":"e_1_3_4_34_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.expneurol.2004.04.017"},{"key":"e_1_3_4_35_1","doi-asserted-by":"publisher","DOI":"10.1038\/nrm3902"},{"key":"e_1_3_4_36_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddr425"},{"key":"e_1_3_4_37_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1155085"},{"key":"e_1_3_4_38_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0140-6736(80)90847-8"},{"key":"e_1_3_4_39_1","article-title":"Analysis of gene expression data using brb-array tools","volume":"3","author":"Richard S","year":"2007","unstructured":"Richard S, , Amy L, , Ming-Chung L, et al. (2007). Analysis of gene expression data using brb-array tools. Cancer Inform, 3, 117693510700300022.","journal-title":"Cancer Inform"},{"key":"e_1_3_4_40_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/4.4.631"},{"key":"e_1_3_4_41_1","doi-asserted-by":"publisher","DOI":"10.3390\/ijms19020390"},{"key":"e_1_3_4_42_1","doi-asserted-by":"publisher","DOI":"10.1093\/glycob\/cwx022"},{"key":"e_1_3_4_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00216-016-9900-6"},{"key":"e_1_3_4_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2017.03.003"},{"key":"e_1_3_4_45_1","doi-asserted-by":"publisher","DOI":"10.1001\/archneurol.2010.239"},{"key":"e_1_3_4_46_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-014-8990-4"},{"key":"e_1_3_4_47_1","doi-asserted-by":"publisher","DOI":"10.1038\/cddis.2014.25"},{"key":"e_1_3_4_48_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuroscience.2016.11.035"},{"key":"e_1_3_4_49_1","doi-asserted-by":"publisher","DOI":"10.1096\/fj.06-7136com"},{"key":"e_1_3_4_50_1","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/ddq337"},{"key":"e_1_3_4_51_1","first-page":"36","article-title":"Glycomics and its application potential in precision medicine","volume":"354","author":"Wang Y","year":"2016","unstructured":"Wang Y, , Adua E, , Russell A, et al. (2016). Glycomics and its application potential in precision medicine. Science, 354, 36\u201339.","journal-title":"Science"},{"key":"e_1_3_4_52_1","doi-asserted-by":"publisher","DOI":"10.1038\/sj.cr.7290318"},{"key":"e_1_3_4_53_1","doi-asserted-by":"publisher","DOI":"10.1111\/ped.13052"},{"key":"e_1_3_4_54_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10571-011-9647-8"}],"container-title":["OMICS: A Journal of Integrative Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/journals.sagepub.com\/doi\/full-xml\/10.1089\/omi.2018.0106","content-type":"application\/xml","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/omi.2018.0106","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/journals.sagepub.com\/doi\/pdf\/10.1089\/omi.2018.0106","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T23:02:16Z","timestamp":1777676536000},"score":1,"resource":{"primary":{"URL":"https:\/\/journals.sagepub.com\/doi\/full\/10.1089\/omi.2018.0106"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2018,9]]},"references-count":53,"journal-issue":{"issue":"9","published-print":{"date-parts":[[2018,9]]}},"alternative-id":["10.1089\/omi.2018.0106"],"URL":"https:\/\/doi.org\/10.1089\/omi.2018.0106","relation":{},"ISSN":["1536-2310","1557-8100"],"issn-type":[{"value":"1536-2310","type":"print"},{"value":"1557-8100","type":"electronic"}],"subject":[],"published":{"date-parts":[[2018,9]]}}}