Multiple System Atrophy: A Sporadic Synucleinopathy
Multiple System Atrophy: A Sporadic Synucleinopathy
复制标题
多系统萎缩：散发性突触核蛋白病
作者：
D. Dickson;Wen‐lang Lin;Wan‐Kyun Liu;S. Yen
多系统萎缩(MSA)是一种散发性神经退行性疾病，临床上以不同程度的帕金森病、小脑性共济失调和自主神经功能障碍为特征，病理上表现为黑质、壳核、橄榄核、桥核和小脑的变性。除了选择性神经元丢失、铁色素堆积和胶质增生外，髓鞘病理也越来越为人们所认识。在受影响的白质中，髓鞘显示出变性的迹象，少突胶质细胞含有嗜银包涵体，即所谓的胶质细胞质包涵体(GCI)。GCI由直径10-15 nm的包被丝组成，泛素和α-突触核蛋白免疫反应阳性。在MSA的神经元胞体和细胞突起中偶见类似的包涵体。鉴于由突触核蛋白组成的包涵体的存在，有理由认为在MSA中突触核蛋白会检测到生化变化，事实上就是这种情况。在MSA中，突触核蛋白的生物物理性质表明不溶性增加，例如在蔗糖梯度中以致密组分沉淀，并可随时提取成洗涤剂和甲酸。令人惊讶的是，突触核蛋白中的这些生化修饰在大脑中比明显的病理变化更普遍，表明了这种疾病的基本分子特征。在路易体病中也检测到类似的神经元包涵体，但不太常见的神经胶质包涵体，那里也有证据表明突触核蛋白发生了生物物理变化。因此，MSA和LBD都是共核病，它们可能包括疾病谱的不同极端，包括散发性疾病和遗传决定的疾病，如家族性路易体帕金森综合症。
Multiple system atrophy (MSA) is a sporadic neurodegenerative disease characterized clinically by varying degrees of Parkinsonism, cerebellar ataxia and autonomic dysfunction and pathologically by degeneration in the substantia nigra, putamen, olivary nucleus, pontine nuclei and cerebellum. In addition to selective neuronal loss, iron pigment accumulation and gliosis, myelin pathology is increasingly recognized. In affected white matter, myelin displays signs of degeneration and oligodendroglia contain argyrophilic inclusion bodies, so‐called glial cytoplasmic inclusions (GCI). GCI are composed of 10–15‐nm diameter coated filaments that are immunoreactive for ubiquitin and α‐synuclein. Similar inclusions are occasionally found in neuronal cell bodies and cell processes in MSA. Given the presence of inclusion bodies composed of synuclein, it is reasonable to assume that biochemical alterations would be detected in synuclein in MSA and indeed this is the case. In MSA synuclein has biophysical properties that suggest increasing insolubility such as sedimentation in dense fractions in sucrose gradients and ready extraction into detergents and formic acid. Surprisingly, these biochemical modifications in synuclein are more widespread in the brain that the obvious pathology and suggest a fundamental molecular characteristic of the disorder. Similar neuronal, and less frequently glial, inclusions are detected in Lewy body disease, where there is also evidence for biophysical alterations in synuclein. Thus, MSA and LBD are both synucleinopathies, and they may comprise different poles of a disease spectrum that includes sporadic disorders as well as genetically determined disorders such as familial Lewy body Parkinsonism.
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来自阿尔茨海默病大脑的异常 tau 蛋白。
DOI：
--
发表时间：
1991
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Liu,WK;Ksiezak-Reding,H;Yen,SH
通讯作者：
Yen,SH
DOI：
--
发表时间：
1998-04
期刊：
The American journal of pathology
影响因子：
--
作者：
M. Baba;S. Nakajo;Ping-Hui Tu;T. Tomita;K. Nakaya;V. Lee;J. Trojanowski;T. Iwatsubo
通讯作者：
M. Baba;S. Nakajo;Ping-Hui Tu;T. Tomita;K. Nakaya;V. Lee;J. Trojanowski;T. Iwatsubo
影响因子：
2.9
作者：
Weinreb, PH;Zhen, WG;Lansbury, PT
通讯作者：
Lansbury, PT
神经退行性疾病中 NACP/α-突触核蛋白的异常积累。
DOI：
--
发表时间：
1998
期刊：
The American journal of pathology
影响因子：
--
作者：
Takeda,A;Mallory,M;Sundsmo,M;Honer,W;Hansen,L;Masliah,E
通讯作者：
Masliah,E