A potential link between autoimmunity and neurodegeneration in immune-mediated neurological disease

被引：36

作者：

Lee, Sangmin ^{[1
,2
]}

Xu, Lijing ^{[4
]}

Shin, Yoojin ^{[1
,2
]}

Gardner, Lidia ^{[1
,2
]}

Hartzes, Anastasia ^{[1
,2
]}

Dohan, F. Curtis ^{[3
]}

Raine, Cedric ^{[5
]}

Homayouni, Ramin ^{[4
]}

Levin, Michael C. ^{[1
,2
]}

机构：

[1] Univ Tennessee, Hlth Sci Ctr, Dept Neurol, Memphis, TN 38163 USA

[2] Vet Adm Med Ctr, Memphis, TN 38104 USA

[3] Univ Tennessee, Hlth Sci Ctr, Dept Pathol, Memphis, TN 38163 USA

[4] Univ Memphis, Bioinformat Program, Memphis, TN 38152 USA

[5] Albert Einstein Coll Med, Dept Neuropathol, Bronx, NY 10461 USA

来源：

JOURNAL OF NEUROIMMUNOLOGY | 2011年 / 235卷 / 1-2期

关键词：

Neurodegeneration; Autoimmunity; Multiple sclerosis; Spastin; Bioinformatics; STIFF PERSON SYNDROME; CORD AXONAL LOSS; MULTIPLE-SCLEROSIS; MOLECULAR MIMICRY; CEREBROSPINAL-FLUID; MEDICAL PROGRESS; T-CELLS; B-CELLS; ANTIBODIES; PROTEIN;

D O I：

10.1016/j.jneuroim.2011.02.007

中图分类号：

R392 [医学免疫学]; Q939.91 [免疫学];

学科分类号：

100102 ;

摘要：

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. Published by Elsevier B.V.

引用

页码：56 / 69

页数：14

共 91 条

[1] Transient axonal injury in the absence of demyelination:: A correlate of clinical disease in acute experimental autoimmune encephalomyelitis [J].

Aboul-Enein, F ;

Weiser, P ;

Höftberger, R ;

Lassmann, H ;

Bradl, M .

ACTA NEUROPATHOLOGICA, 2006, 111 (06) :539-547

[2] ANTIBODIES TO OLIGODENDROGLIA IN PATIENTS WITH MULTIPLE-SCLEROSIS [J].

ABRAMSKY, O ;

LISAK, RP ;

SILBERBERG, DH ;

PLEASURE, DE .

NEW ENGLAND JOURNAL OF MEDICINE, 1977, 297 (22) :1207-1211

[3] Antibodies to recoverin induce apoptosis of photoreceptor and bipolar cells in vivo [J].

Adamus, G ;

Machnicki, M ;

Elerding, H ;

Sugden, B ;

Blocker, YS ;

Fox, DA .

JOURNAL OF AUTOIMMUNITY, 1998, 11 (05) :523-533

[4] Identification of nuclear localisation sequences in spastin (SPG4) using a novel Tetra-GFP reporter system [J].

Beetz, C ;

Brodhun, M ;

Mountzouris, K ;

Kiehntopf, M ;

Berndt, A ;

Lehnert, D ;

Deufel, T ;

Bastmeyer, M ;

Schickel, J .

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS, 2004, 318 (04) :1079-1084

[5]

Bjartmar C, 2000, ANN NEUROL, V48, P893, DOI 10.1002/1531-8249(200012)48:6<893::AID-ANA10>3.3.CO

[6]

2-2

[7] Axonal loss in the pathology of MS: consequences for understanding the progressive phase of the disease [J].

Bjartmar, C ;

Wujek, JR ;

Trapp, BD .

JOURNAL OF THE NEUROLOGICAL SCIENCES, 2003, 206 (02) :165-171

[8] Time course and distribution of inflammatory and neurodegenerative events suggest structural bases for the pathogenesis of experimental autoimmune encephalomyelitis [J].

Brown, David A. ;

Sawchenko, Paul E. .

JOURNAL OF COMPARATIVE NEUROLOGY, 2007, 502 (02) :236-260

[9] Spastin subcellular localization is regulated through usage of different translation start sites and active export from the nucleus [J].

Claudiani, P ;

Riano, E ;

Errico, A ;

Andolfi, G ;

Rugarli, EI .

EXPERIMENTAL CELL RESEARCH, 2005, 309 (02) :358-369

[10] The alternative splicing repressors hnRNP A1/A2 and PTB influence pyruvate kinase isoform expression and cell metabolism [J].

Clower, Cynthia V. ;

Chatterjee, Deblina ;

Wang, Zhenxun ;

Cantley, Lewis C. ;

Heiden, Matthew G. Vander ;

Krainer, Adrian R. .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2010, 107 (05) :1894-1899

← 1 2 3 4 5 6 7 8 9 10 →