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
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
收藏
页码:56 / 69
页数:14
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