title: A potential link between autoimmunity and neurodegeneration in immune-mediated neurological disease.
abstract: Multiple sclerosis (MS) patients make antibodies to heterogeneous nuclear ribonuclear protein A1 (hnRNP-A1), a nucleocytoplasmic protein. We hypothesized this autoimmune reaction might contribute to neurodegeneration. Antibodies from MS patients reacted with hnRNP-A1-'M9', its nuclear translocation sequence. Transfection of anti-M9 antibodies into neurons resulted in neuronal injury and changes in transcripts related to hnRNP-A1 function. Importantly, RNA levels for the spinal paraplegia genes (SPGs) decreased. Changes in SPG RNA levels were confirmed in neurons purified from MS brains. Also, we show molecular interactions between spastin (the encoded protein of SPG4) and hnRNP-A1. These data suggest a link between autoimmunity, clinical phenotype and neurodegeneration in MS.
authors.affiliation: Veterans Administration Medical Center, 1030 Jefferson Avenue, Memphis, TN 38104, USA.
authors.forename: Sangmin
authors.initials: S
authors.lastname: Lee
authors.forename: Lijing
authors.initials: L
authors.lastname: Xu
authors.forename: Yoojin
authors.initials: Y
authors.lastname: Shin
authors.forename: Lidia
authors.initials: L
authors.lastname: Gardner
authors.forename: Anastasia
authors.initials: A
authors.lastname: Hartzes
authors.forename: F Curtis
authors.initials: FC
authors.lastname: Dohan
authors.forename: Cedric
authors.initials: C
authors.lastname: Raine
authors.forename: Ramin
authors.initials: R
authors.lastname: Homayouni
authors.forename: Michael C
authors.initials: MC
authors.lastname: Levin
mesh_terms: D000328:Adult; D000368:Aged; D020274:Autoimmune Diseases of the Nervous System / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D002460:Cell Line; D002478:Cells, Cultured; D002540:Cerebral Cortex / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D005260:Female; D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B / Q000096:biosynthesis*; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000276:immunology* / Q000378:metabolism* / Q000473:pathology; D009410:Nerve Degeneration / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D055815:Young Adult
chemical_list: D000076245:Heterogeneous Nuclear Ribonucleoprotein A1; D034481:Heterogeneous-Nuclear Ribonucleoprotein Group A-B