Neurodegeneration with brain iron accumulation, type 1 is characterized by α-, β-, and γ-synuclein neuropathology

作     者：Galvin, JE Giasson, B Hurtig, HI Lee, VMY Trojanowski, JQ 

作者机构：Univ Penn Sch Med Ctr Neurodegenerat Dis Res Dept Pathol & Lab Med Philadelphia PA 19104 USA Univ Penn Dept Neurol Philadelphia PA 19104 USA Med Coll Penn & Hahnemann Univ Dept Neurol Philadelphia PA 19102 USA 

出 版 物：《AMERICAN JOURNAL OF PATHOLOGY》 (美国病理学杂志)

年 卷 期：2000年第157卷第2期

页      面：361-368页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 10[医学] 

基　　金：NICHD NIH HHS [N01-HD-8-3284] Funding Source: Medline 

主　　题：淀粉样β肽类/分析 印迹法 蛋白质 脑/代谢 脑/病理学 致命性结局 免疫组织化学 铁/代谢 神经组织蛋白质类/分析 神经变性疾病/代谢 神经变性疾病/病理学 突触核蛋白类 α突触核蛋白 β突触核蛋白 γ突触核蛋白 tau蛋白质类/分析 青少年 老年人 人类 婴儿 

摘      要：Neurodegeneration with brain iron accumulation, type 1 (NBIA 1), or Hallervorden-Spatz syndrome, is a rare neurodegenerative disorder characterized clinically by Parkinsonism, cognitive impairment, pseudobulbar features, as well as cerebellar ataxia, and neuropathologically by neuronal loss, gliosis, and iron deposition in the globus pallidus, red nucleus, and substantia nigra. The hallmark pathological lesions of NBIA 1 are axonal spheroids, but Lewy body (LB)-like intraneuronal inclusions, glial inclusions, and rare neurofibrillary tangles also occur. Here we show that there is an accumulation of alpha-synuclein (alpha S) in LB-like inclusions, glial inclusions, and spheroids in the brains of three NBIA 1 patients. Further, beta-synuclein (beta S) and gamma-synuclein (gamma S) immunoreactivity was detected in spheroids but not in LB-like or glial inclusions. Western blot analysis demonstrated high-molecular weight alpha S aggregates in the high-salt-soluble and Triton X-100-insoluble/sodium dodecyl sulfate-soluble fraction of the NBIA 1 brain. Significantly, the levels of alpha S were markedly reduced in the Triton X-100-soluble fractions compared to control brain, and unlike other synucleinopathies, insoluble alpha S did not accumulate in the formic acid-soluble fraction. These findings expand the concept of neurodegenerative synucleinopathies by Implicating alpha S, beta S, and gamma S in the pathogenesis of NBIA 1.