Size-dependent neurotoxicity of beta-amyloid oligomers.
Size-dependent neurotoxicity of beta-amyloid oligomers.
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DOI：
10.1016/j.abb.2010.02.001
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发表时间：
2010-04-15
影响因子：
3.9
通讯作者：
Borutaite, Vilmante
中科院分区：
文献类型：
--
作者：
Cizas, Paulius;Budvytyte, Rima;Morkuniene, Ramune;Moldovan, Radu;Broccio, Matteo;Loesche, Mathias;Niaura, Gediminas;Valincius, Gintaras;Borutaite, Vilmante
关键词：
研究了可溶性β淀粉样蛋白（Aβ）寡聚体的大小与其对大鼠小脑颗粒细胞（CGC）毒性的关系。Aβ1-42体外寡聚化过程中条件的变化导致肽组装体具有不同的颗粒大小，这通过原子力显微镜测量并通过动态光散射和荧光相关光谱法证实。平均颗粒z高度为1-2 nm的Aβ1-42的小寡聚体表现出与磷脂囊泡结合的倾向，并且它们是在亚微摩尔浓度下诱导快速神经元坏死的毒性最强的物质，而较大的聚集体（z高度高于4-5 nm）不与囊泡结合，也不引起可检测的神经元死亡。在皮层神经元的原代培养物中也观察到类似的神经毒性模式，而Aβ1-42寡聚体、单体和原纤维对CGC培养物或巨噬细胞J774细胞中的胶质细胞无毒性。然而，两种寡聚体形式的Aβ1-42均诱导CGC培养物中神经元细胞密度降低。
The link between the size of soluble amyloid β (Aβ) oligomers and their toxicity to rat cerebellar granule cells (CGC) was investigated. Variation in conditions during in vitro oligomerization of Aβ1-42 resulted in peptide assemblies with different particle size as measured by atomic force microscopy and confirmed by the dynamic light scattering and fluorescence correlation spectroscopy. Small oligomers of Aβ1-42 with a mean particle z-height of 1-2 nm exhibited propensity to bind to the phospholipid vesicles and they were the most toxic species that induced rapid neuronal necrosis at submicromolar concentrations whereas the bigger aggregates (z-height above 4-5 nm) did not bind vesicles and did not cause detectable neuronal death. Similar neurotoxic pattern was also observed in primary cultures of cortex neurons whereas Aβ1–42 oligomers, monomers and fibrils were non-toxic to glial cells in CGC cultures or macrophage J774 cells. However, both oligomeric forms of Aβ1-42 induced reduction of neuronal cell densities in the CGC cultures.
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