PMID- 24067896 OWN - NLM STAT- MEDLINE DCOM- 20150330 LR - 20220129 IS - 1477-0970 (Electronic) IS - 1352-4585 (Linking) VI - 20 IP - 6 DP - 2014 May TI - Reductions in neuronal peroxisomes in multiple sclerosis grey matter. PG - 651-9 LID - 10.1177/1352458513505691 [doi] AB - BACKGROUND: Peroxisomes are organelles in eukaryotic cells with multiple functions including the detoxification of reactive oxygen species, plasmalogen synthesis and beta-oxidation of fatty acids. Recent evidence has implicated peroxisomal dysfunction in models of multiple sclerosis (MS) disease progression. OBJECTIVES: Our aims were to determine whether there are changes in peroxisomes in MS grey matter (GM) compared to control GM. METHODS: We analysed cases of MS and control GM immunocytochemically to assess peroxisomal membrane protein (PMP70) and neuronal proteins. We examined the expression of ABCD3 (the gene that encodes PMP70) in MS and control GM. Analyses of very long chain fatty acid (VLCFA) levels in GM were performed. RESULTS: PMP70 immunolabelling of neuronal somata was significantly lower in MS GM compared to control. Calibration of ABCD3 gene expression with reference to glyceraldehyde 3-phsophate dehydrogenase (GAPDH) revealed overall decreases in expression in MS compared to controls. Mean PMP70 counts in involved MS GM negatively correlated to disease duration. Elevations in C26:0 (hexacosanoic acid) were found in MS GM. CONCLUSIONS: Collectively, these observations provide evidence that there is an overall reduction in peroxisomal gene expression and peroxisomal proteins in GM neurons in MS. Changes in peroxisomal function may contribute to neuronal dysfunction and degeneration in MS. FAU - Gray, Elizabeth AU - Gray E AD - MS and Stem Cell Labs, University of Bristol, UK. FAU - Rice, Claire AU - Rice C FAU - Hares, Kelly AU - Hares K FAU - Redondo, Juliana AU - Redondo J FAU - Kemp, Kevin AU - Kemp K FAU - Williams, Marcus AU - Williams M FAU - Brown, Ann AU - Brown A FAU - Scolding, Neil AU - Scolding N FAU - Wilkins, Alastair AU - Wilkins A LA - eng GR - G-0909/PUK_/Parkinson's UK/United Kingdom GR - MR/K004166/1/MRC_/Medical Research Council/United Kingdom PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20130925 PL - England TA - Mult Scler JT - Multiple sclerosis (Houndmills, Basingstoke, England) JID - 9509185 RN - 0 (ABCD3 protein, human) RN - 0 (ATP-Binding Cassette Transporters) RN - 0 (Membrane Proteins) SB - IM MH - ATP-Binding Cassette Transporters/metabolism MH - Adult MH - Aged MH - Aged, 80 and over MH - Female MH - Gene Expression/physiology MH - Gray Matter/metabolism/*pathology MH - Humans MH - Male MH - Membrane Proteins/*metabolism MH - Middle Aged MH - Multiple Sclerosis/*pathology MH - Neurons/metabolism/*pathology MH - Peroxisomes/*pathology OTO - NOTNLM OT - Peroxisomes OT - grey matter OT - multiple sclerosis EDAT- 2013/09/27 06:00 MHDA- 2015/03/31 06:00 CRDT- 2013/09/27 06:00 PHST- 2013/09/27 06:00 [entrez] PHST- 2013/09/27 06:00 [pubmed] PHST- 2015/03/31 06:00 [medline] AID - 1352458513505691 [pii] AID - 10.1177/1352458513505691 [doi] PST - ppublish SO - Mult Scler. 2014 May;20(6):651-9. doi: 10.1177/1352458513505691. Epub 2013 Sep 25.