α-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseases
α-Internexin aggregates are abundant in neuronal intermediate filament inclusion disease (NIFID) but rare in other neurodegenerative diseases
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DOI：
10.1007/s00401-004-0882-7
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发表时间：
2004-09-01
影响因子：
12.7
通讯作者：
Trojanowski, JQ
中科院分区：
文献类型：
--
作者：
Cairns, NJ;Uryu, K;Trojanowski, JQ
α-internexin 和三个神经丝 (NF) 亚基 NF-L、NF-M 和 NF-H 的异常神经元聚集体最近被确定为神经元中间丝 (IF) 包涵体病 (NIFID) 的病理标志，NIFID 是一种新型的早发性神经系统疾病，具有多种临床表型，包括额颞叶痴呆、锥体痴呆和痴呆。 锥体外系体征。 α-Internexin 是一种 IV 类 IF 蛋白，是 NIFID 内含物的主要成分，此前尚未被鉴定为任何其他神经退行性疾病的病理蛋白聚集体的成分。因此，为了确定该蛋白的特异性，我们对 NIFID、非 tau 额颞叶痴呆、运动神经元疾病、α-突触核蛋白病、tau蛋白病和正常老年对照脑的病例进行了 α-internexin 免疫组织化学分析。我们的结果表明，IV 类 IF 蛋白存在于所有 NIFID 病例的多形性包涵体中。阿尔茨海默氏病、路易体病和运动神经元病中的一小部分异常神经元包涵体也含有 α-internexin 表位。因此，α-internexin 是 NIFID 中神经元包涵体的主要成分，并且是其他神经退行性疾病中包涵体的相对次要成分。神经元细胞质包涵体中α-internexin的发现暗示了NIFID和其他具有病理性丝状神经元包涵体的神经系统疾病的发病机制。
Abnormal neuronal aggregates of alpha-internexin and the three neurofilament (NF) subunits, NF-L, NF-M, and NF-H have recently been identified as the pathological hallmarks of neuronal intermediate filament (IF) inclusion disease (NIFID), a novel neurological disease of early onset with a variable clinical phenotype including frontotemporal dementia, pyramidal and extrapyramidal signs. alpha-Internexin, a class IV IF protein, a major component of inclusions in NIFID, has not previously been identified as a component of the pathological protein aggregates of any other neurodegenerative disease. Therefore, to determine the specificity of this protein, alpha-internexin immunohistochemistry was undertaken on cases of NIFID, non-tau frontotemporal dementias, motor neuron disease, alpha-synucleinopathies, tauopathies, and normal aged control brains. Our results indicate that class IV IF proteins are present within the pleomorphic inclusions of all cases of NIFID. Small subsets of abnormal neuronal inclusions in Alzheimer's disease, Lewy body diseases, and motor neuron disease also contain epitopes of alpha-internexin. Thus, alpha-internexin is a major component of the neuronal inclusions in NIFID and a relatively minor component of inclusions in other neurodegenerative diseases. The discovery of alpha-internexin in neuronal cytoplasmic inclusions implicates novel mechanisms of pathogenesis in NIFID and other neurological diseases with pathological filamentous neuronal inclusions.