Beta-synuclein occurs in vivo in lipid-associated oligomers and forms hetero-oligomers with alpha-synuclein.
Beta-synuclein occurs in vivo in lipid-associated oligomers and forms hetero-oligomers with alpha-synuclein.
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DOI：
10.1111/j.1471-4159.2008.05776.x
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发表时间：
2009-01
影响因子：
4.7
通讯作者：
Sharon R
中科院分区：
文献类型：
--
作者：
Israeli E;Sharon R
α-突触核蛋白（αS）和β-突触核蛋白（βS）是参与帕金森病和相关突触核蛋白病的同源蛋白。虽然αS具有神经毒性，其在路易小体中的聚集和沉积与神经变性有关，但βS被认为是αS聚集和毒性的有效抑制剂。关于βS的神经保护作用机制，目前尚无报道。在这里，我们报道了与αS类似，βS通常出现在wt小鼠大脑中脂相关的可溶性低聚物中。采用尺寸排除法和离子交换色谱法从小鼠全脑中部分纯化了βS和αS蛋白，发现了高度相似的洗脱谱。利用该技术，我们能够将βS与αS部分分离，并进一步将βS单体与αS自身的低聚物分离。重要的是，我们发现尽管αS和βS具有高度的相似性，但βS的寡聚不受细胞多不饱和脂肪酸（PUFA）水平增加的影响，而αS的寡聚却被PUFA显著增强。我们发现αS和βS的异低聚物在体内存在，并表明βS的表达抑制pufa增强的αS寡聚物，形成的异低聚物高达四分之一，不会进一步繁殖。
α-synuclein (αS) and β-synuclein (βS) are homologous proteins implicated in Parkinson’s disease and the related synucleinopathies. While αS is neurotoxic and its aggregation and deposition in Lewy bodies is related to neurodegeneration, βS is considered a potent inhibitor of αS aggregation and toxicity. No mechanism for the neuroprotective role of βS has been described before. Here we report that similar to αS, βS normally occurs in lipid-associated, soluble oligomers in wt mouse brains. We partially purified βS and αS proteins from whole mouse brain by size exclusion followed by ion exchange chromatography and found highly similar elution profiles. Using this technique, we were able to partially separate βS from αS and further separate βS monomer from its own oligomers. Importantly, we show that although αS and βS share high degree of similarities, βS oligomerization is not affected by increasing cellular levels of PolyUnsaturated Fatty Acids (PUFA), while αS oligomerization is dramatically enhanced by PUFA. We show the in vivo occurrence of hetero oligomers of αS and βS and suggest that βS expression inhibits PUFA-enhanced αS oligomerization by forming hetero-oligomers up to a quatramer that do not further propagate.
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影响因子：
4.8
作者：
Hashimoto, M;Bar-on, P;Masliah, E
通讯作者：
Masliah, E
影响因子：
16.2
作者：
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通讯作者：
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作者：
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