eprintid: 177309
rev_number: 193
eprint_status: archive
userid: 608
dir: disk0/00/17/73/09
datestamp: 2010-11-04 21:42:56
lastmod: 2021-09-19 23:03:06
status_changed: 2012-03-20 10:06:46
type: article
metadata_visibility: show
item_issues_count: 0
creators_name: Petzold, A
creators_name: Gveric, D
creators_name: Groves, M
creators_name: Schmierer, K
creators_name: Grant, D
creators_name: Chapman, M
creators_name: Keir, G
creators_name: Cuzner, L
creators_name: Thompson, EJ
title: Phosphorylation and compactness of neurofilaments in multiple sclerosis: Indicators of axonal pathology
ispublished: pub
divisions: UCL
divisions: B02
divisions: C07
divisions: D07
keywords: neurofilament phosphoforms, multiple sclerosis, axonal injury, WALLERIAN DEGENERATION, WHITE-MATTER, NOGO-A, GLUTAMATE, DAMAGE, LESIONS, PROTEINS, DISEASE, INJURY, NEURODEGENERATION
abstract: Aims: Axonal pathology extends to the axonal cytoarchitecture leaving its Signature on axoskeletal proteins. This study investigated whether neurofilament (NfH) phosphorylation would relate to the dynamics of axonal pathology in multiple sclerosis (MS).Methods: NfH phosphoforms (SM132, SM134, SM135) were quantified by ELISA from microdissected samples of control and MS brain and spinal cord. Individual axons were analysed by electron microscopy, densitometrically and morphologically in adjacent tissue sections. Experiments were Carried Out pre- and post enzymatic dephosphorylation.Results: In control tissue a rostro-caudal gradient of NfH indicated an increase in axonal density from the brain gray matter towards the spinal cord. The highest levels of phosphorylated and hyperphosphorylated NfH were found in acute lesions of brain and spinal cord, in contrast to chronic lesions where levels were lower than in white matter, consistent with axonal loss. Dephosphorylated NfH was higher, but less densly packed in MS white matter axons compared to control tissue.Conclusions: The findings suggest that a less organised/compact axoskeleton or impaired axonal transport may represent an early sign of axonal pathology within the normal appearing white matter in MS. Subsequently a proportional increase of dephosphorylated NfH, aberrant phosphorylation and/or aggregation may occur whilst the protein is transported through the white matter towards the MS plaque, where hyperphosphorylated NfH dominates. (c) 2008 Elsevier Inc. All rights reserved.
date: 2008-10
publisher: ACADEMIC PRESS INC ELSEVIER SCIENCE
official_url: http://dx.doi.org/10.1016/j.expneurol.2008.06.008
vfaculties: VFBRS
oa_status: green
pmcid: PMC2583254
language: eng
primo: open
primo_central: open_green
article_type_text: Article
verified: verified_batch
elements_source: Web of Science
elements_id: 96188
doi: 10.1016/j.expneurol.2008.06.008
language_elements: EN
lyricists_name: Chapman, Miles
lyricists_name: Cuzner, Margaret
lyricists_name: Groves, Michael
lyricists_name: Keir, Geoffrey
lyricists_name: Petzold, Axel
lyricists_name: Schmierer, Klaus
lyricists_name: Thompson, Edward
lyricists_id: MDCHA44
lyricists_id: MLCUZ52
lyricists_id: MJGRO65
lyricists_id: GKEIR26
lyricists_id: APETZ95
lyricists_id: KSCHM30
lyricists_id: EJTHO52
full_text_status: public
publication: Experimental Neurology
volume: 213
number: 2
pagerange: 326 - 335
issn: 0014-4886
citation:        Petzold, A;    Gveric, D;    Groves, M;    Schmierer, K;    Grant, D;    Chapman, M;    Keir, G;         ... Thompson, EJ; + view all <#>        Petzold, A;  Gveric, D;  Groves, M;  Schmierer, K;  Grant, D;  Chapman, M;  Keir, G;  Cuzner, L;  Thompson, EJ;   - view fewer <#>    (2008)    Phosphorylation and compactness of neurofilaments in multiple sclerosis: Indicators of axonal pathology.                   Experimental Neurology , 213  (2)   326 - 335.    10.1016/j.expneurol.2008.06.008 <https://doi.org/10.1016/j.expneurol.2008.06.008>.       Green open access   
 
document_url: https://discovery.ucl.ac.uk/id/eprint/177309/1/177309_ms6-nfh-PR-v9k.pdf