Machado-Joseph disease/spinocerebellar ataxia type 3.
Machado-Joseph disease/spinocerebellar ataxia type 3.
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DOI：
10.1016/b978-0-444-51892-7.00027-9
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发表时间：
2012
影响因子：
--
通讯作者：
Paulson, Henry
中科院分区：
文献类型：
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作者：
Paulson, Henry
Machado Joseph病（MJD），也被称为脊髓小脑性共济失调3型（SCA3），可能是世界上最常见的显性遗传性共济失调。在这里，我将回顾MJD的历史、临床、神经病理、遗传和致病特征，并以简要讨论目前和可能的未来治疗这种目前无法治愈的疾病结束。与许多其他显性遗传性共济失调一样，MJD/SCA3表现出显著的临床异质性，反映了潜在的遗传缺陷：一个不稳定的CAG三核苷酸重复序列，在受影响的人群中大小不同。MJD/SCA3中的这种致病性重复序列编码疾病蛋白中氨基酸谷氨酰胺的扩展区，称为ataxin-3。MJD/SCA3是九种已知的多谷氨酰胺神经退行性疾病之一，其发病机制以蛋白质错误折叠和积累为中心。MJD/SCA3及其疾病蛋白的特性根据已知的整个类多聚谷氨酰胺疾病进行了讨论。
Machado Joseph disease (MJD), also known as Spinocerebellar ataxia type 3 (SCA3), may be the most common dominantly inherited ataxia in the world. Here I will review historical, clinical, neuropathological, genetic and pathogenic features of MJD, and finish with a brief discussion of present, and possible future, treatment for this currently incurable disorder. Like many other dominantly inherited ataxias, MJD/SCA3 shows remarkable clinical heterogeneity, reflecting the underlying genetic defect: an unstable CAG trinucleotide repeat that varies in size among affected persons. This pathogenic repeat in MJD/SCA3 encodes an expanded tract of the amino acid glutamine in the disease protein, which is known as ataxin-3. MJD/SCA3 is one of nine identified polyglutamine neurodegenerative diseases which share features of pathogenesis centered on protein misfolding and accumulation. The specific properties of MJD/SCA3 and its disease protein are discussed in light to what is known about the entire class of polyglutamine diseases.