{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,21]],"date-time":"2026-09-21T17:00:11Z","timestamp":1790010011029,"version":"4.0.1"},"reference-count":60,"publisher":"Wiley","issue":"5","license":[{"start":{"date-parts":[[2015,7,1]],"date-time":"2015-07-01T00:00:00Z","timestamp":1435708800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001518","name":"Maurice and Phyllis Paykel Trust","doi-asserted-by":"crossref","award":["3625842"],"award-info":[{"award-number":["3625842"]}],"id":[{"id":"10.13039\/501100001518","id-type":"DOI","asserted-by":"crossref"}]},{"name":"University of Auckland Postgraduate Scholarship"},{"name":"School of Medical Sciences Writing Fellowship"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Journal of Neurochemistry"],"published-print":{"date-parts":[[2015,9]]},"abstract":"Abstract<\/jats:title>Huntington's disease (HD<\/jats:styled-content>) is an autosomal dominant neurodegenerative disease caused by an expansion of theCAG<\/jats:styled-content>repeat in the huntingtin gene. One of the brain changes that occurs inHD<\/jats:styled-content>is the expression of the receptor for advanced glycation end products (RAGE<\/jats:styled-content>), a receptor protein capable of activating multiple signalling pathways by interacting with a range of ligands leading to either beneficial or harmful effects to the cell. Here, we demonstrate in humanHD<\/jats:styled-content>brains a high degree of co\u2010localization ofRAGE<\/jats:styled-content>with its putative ligands S100B and N\u2010carboxymethyllysine (CML<\/jats:styled-content>) in the caudate nucleus (CN<\/jats:styled-content>) and the subependymal layer (SEL<\/jats:styled-content>). The level of co\u2010staining for bothRAGE<\/jats:styled-content>\u2010S100B andRAGE<\/jats:styled-content>\u2010CML<\/jats:styled-content>was the highest in the astrocytes but was low in neurons and microglia. The immunostaining forRAGE<\/jats:styled-content>, S100B andCML<\/jats:styled-content>extended in a medio\u2010lateral (SEL<\/jats:styled-content>\u2010CN<\/jats:styled-content>) direction with increasing grade, such that any change in the expression and co\u2010localization pattern between grades was less prominent in the lateralCN<\/jats:styled-content>. Additionally, signalling molecules that are downstream ofRAGE<\/jats:styled-content>activation showed changes in their activation status inHD<\/jats:styled-content>brains. A larger number ofRAGE<\/jats:styled-content>\u2010positive astrocytic cells hadNF<\/jats:styled-content>\u2010kB<\/jats:styled-content>translocated to the nucleus and the level of phospho\u2010ERK<\/jats:styled-content>1\/2 was also increased inHD<\/jats:styled-content>brains. Interestingly, the level ofmD<\/jats:styled-content>ia\u20101, that interacts directly with the cytoplasmic domain ofRAGE<\/jats:styled-content>, decreased inHD<\/jats:styled-content>. Overall, the results suggest a correlation between the functions ofRAGE<\/jats:styled-content>and theHD<\/jats:styled-content>pathology, but the influence ofRAGE<\/jats:styled-content>on astrocytes and the impact of this onHD<\/jats:styled-content>progression requires further study.<\/jats:p><\/jats:sec>image<\/jats:alt-text><\/jats:graphic><\/jats:boxed-text>RAGE (receptor for advanced glycation end products) binds multiple types of ligand to produce either neurotrophic or neurotoxic effects. Immunohistochemical staining of HD human brains showed that both RAGE and its ligands were expressed primarily in astrocytes. The pattern of staining corresponded to the grade and region\u2010wise pattern of neurodegeneration suggesting a possible role for RAGE in HD pathology.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jnc.13178","type":"journal-article","created":{"date-parts":[[2015,5,25]],"date-time":"2015-05-25T04:39:35Z","timestamp":1432528775000},"page":"927-942","source":"Crossref","is-referenced-by-count":34,"title":["The RAGE receptor and its ligands are highly expressed in astrocytes in a grade\u2010dependant manner in the striatum and subependymal layer in Huntington's disease"],"prefix":"10.1111","volume":"134","author":[{"given":"Joanne","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Anatomy with Radiology Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"},{"name":"Centre for Brain Research Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henry J.","family":"Waldvogel","sequence":"additional","affiliation":[{"name":"Department of Anatomy with Radiology Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"},{"name":"Centre for Brain Research Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard L. M.","family":"Faull","sequence":"additional","affiliation":[{"name":"Department of Anatomy with Radiology Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"},{"name":"Centre for Brain Research Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maurice A.","family":"Curtis","sequence":"additional","affiliation":[{"name":"Department of Anatomy with Radiology Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"},{"name":"Centre for Brain Research Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Louise F. B.","family":"Nicholson","sequence":"additional","affiliation":[{"name":"Department of Anatomy with Radiology Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"},{"name":"Centre for Brain Research Faculty of Medical and Health Science (FMHS) University of Auckland Auckland New Zealand"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2015,7]]},"reference":[{"key":"e_1_2_7_2_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.brainresbull.2011.01.009"},{"key":"e_1_2_7_3_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M406440200"},{"key":"e_1_2_7_4_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf180"},{"key":"e_1_2_7_5_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1474-9726.2010.00556.x"},{"key":"e_1_2_7_6_1","doi-asserted-by":"crossref","first-page":"12669","DOI":"10.1016\/S0021-9258(18)31440-6","article-title":"S\u2010100 protein, but not calmodulin, binds to the glial fibrillary acidic protein and inhibits its polymerization in a Ca(2+)\u2010dependent manner","volume":"15","author":"Bianchi R.","year":"1993","journal-title":"J. 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