title: Vesicle associated membrane protein B (VAPB) is decreased in ALS spinal cord.
abstract: The aim of this study was to quantify spinal cord expression of genes known to cause familial amyotrophic lateral sclerosis (FALS) or influence survival in a large cohort of sporadic cases of ALS (SALS), in order to determine their relevance to pathogenic mechanisms occurring in SALS. The expression of superoxide dismutase 1 (SOD1), vesicle associated membrane protein (VAPB), senataxin (SETX), dynactin (DCTN1), vascular endothelial growth factor (VEGF), insulin-like growth factor-1 (IGF1), the small heat shock proteins, HSPB1 and HSPB8, and three genes activated during disease progression, caspases-1 and -3 and glial fibrillary acidic protein (GFAP), were quantified. Robust changes in the expression of four genes were found, VAPB mRNA levels were decreased in the spinal cord of ALS patients compared to controls (p<0.006), whilst HSPB1, HSPB8 and caspase-1 showed significant increases (1.5-2.3-fold). Expression of VAPB mRNA and protein was predominantly localised to large motor neurones further supporting the relevance of this finding to disease progression occurring in SALS.
authors.affiliation: Division of Neuroscience and Mental Health, Faculty of Medicine, Imperial College London, London, UK.
authors.forename: Georgia
authors.initials: G
authors.lastname: Anagnostou
authors.forename: Mohammed T
authors.initials: MT
authors.lastname: Akbar
authors.forename: Praveen
authors.initials: P
authors.lastname: Paul
authors.forename: Claire
authors.initials: C
authors.lastname: Angelinetta
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Steiner
authors.forename: Jacqueline
authors.initials: J
authors.lastname: de Belleroche
mesh_terms: D000293:Adolescent; D000328:Adult; D000367:Age Factors; D000690:Amyotrophic Lateral Sclerosis / Q000378:metabolism / Q000473:pathology*; D020170:Caspase 1 / Q000235:genetics / Q000378:metabolism; D002648:Child; D002675:Child, Preschool; D005260:Female; D005786:Gene Expression Regulation / Q000502:physiology*; D055551:HSP27 Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D008875:Middle Aged; D018832:Molecular Chaperones; D009046:Motor Neurons / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism; D011180:Postmortem Changes; D017346:Protein Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012737:Sex Factors; D013116:Spinal Cord / Q000378:metabolism* / Q000473:pathology; D018709:Statistics, Nonparametric; D033921:Vesicular Transport Proteins / Q000235:genetics / Q000378:metabolism*; D055815:Young Adult
chemical_list: D055551:HSP27 Heat-Shock Proteins; C057725:HSPB1 protein, human; C413214:HSPB8 protein, human; D006360:Heat-Shock Proteins; D018832:Molecular Chaperones; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; C496748:VAPB protein, human; D033921:Vesicular Transport Proteins; D017346:Protein Serine-Threonine Kinases; D020170:Caspase 1