The solubility of α-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson's disease
The solubility of α-synuclein in multiple system atrophy differs from that of dementia with Lewy bodies and Parkinson's disease
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DOI：
10.1046/j.1471-4159.2001.00021.x
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发表时间：
2001-01-01
影响因子：
4.7
通讯作者：
Li, QX
中科院分区：
文献类型：
--
作者：
Campbell, BCV;McLean, CA;Li, QX
含有α-突触核蛋白（α SN）的细胞内包涵体是几种神经退行性疾病的特征性特征。包涵体发生在多系统萎缩（MSA）的少突胶质细胞和路易体痴呆（DLB）和帕金森病（PD）的神经元中。为了鉴定aSN的疾病相关变化，本研究比较了来自MSA、DLB、PD和正常老年对照的脑匀浆中aSN的水平、溶解度和分子量种类。在DLB和PD中，与灰质匀浆中的对照相比，检测到大量的洗涤剂可溶性和洗涤剂不溶性α SN。与对照组相比，MSA病例在来自笔和白色物质的脑样本的洗涤剂可溶性部分中具有显著更高水平的α SN，但未检测到洗涤剂不溶性α SN。在个体MSA病例中，α SN的缓冲盐水可溶性和洗涤剂可溶性水平之间呈负相关，表明在疾病中向不溶性转变。疾病中灰质和白色物质之间α SN溶解度的差异可能是由于与少突胶质细胞相比，神经元中α SN的加工不同。高度不溶性的α SN不参与MSA的发病机制。因此，α SN的缓冲盐溶性或去污剂溶性形式可能参与其他α SN相关疾病的发病机制。
Intracellular inclusions containing alpha -synuclein (alpha SN) are pathognomonic features of several neurodegenerative disorders. Inclusions occur in oligodendrocytes in multiple system atrophy (MSA) and in neurons in dementia with Lewy bodies (DLB) and Parkinson's disease (PD). In order to identify disease-associated changes of aSN, this study compared the levels, solubility and molecular weight species of aSN in brain homogenates from MSA, DLB, PD and normal aged controls. In DLB and PD, substantial amounts of detergent-soluble and detergent-insoluble alpha SN were detected compared with controls in grey matter homogenate. Compared with controls, MSA cases had significantly higher levels of alpha SN in the detergent-soluble fraction of brain samples from pens and white matter but detergent-insoluble alpha SN was not detected. There was an inverse correlation between buffered saline-soluble and detergent-soluble levels of alpha SN in individual MSA cases suggesting a transition towards insolubility in disease. The differences in solubility of alpha SN between grey and white matter in disease may result from different processing of alpha SN in neurons compared with oligodendrocytes. Highly insoluble alpha SN is not involved in the pathogenesis of MSA. It is therefore possible that buffered saline-soluble or detergent-soluble forms of alpha SN are involved in the pathogenesis of other alpha SN-related diseases.