A thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific neurotoxicity
A thrombin cleavage fragment of apolipoprotein E exhibits isoform-specific neurotoxicity
复制标题
DOI：
10.1097/00001756-199611040-00025
复制
发表时间：
1996-11-04
期刊：
影响因子：
1.7
通讯作者：
Crutcher, KA
中科院分区：
文献类型：
--
作者：
Marques, MA;Tolar, M;Crutcher, KA
一个22 kDa的载脂蛋白E片段含有一个假定的细胞毒性结构域被确定在死后人脑组织和新鲜的CSF。该片段显然等同于主要的apoE凝血酶裂解产物。体外毒性试验表明，来自重组表达的人apoE的相应片段对培养物中的原代神经元是有毒的，并且E4衍生的片段比来自E3同种型的片段毒性更大。这些结果表明，apoE的蛋白水解片段可能在与AD和apoE相关的其他疾病的病理学中发挥直接作用。
A 22 kDa fragment of apoE containing a putative cytotoxi domain was identified in postmortem human brain tissue and fresh CSF. This fragment is apparently equivalent to the major apoE thrombin cleavage product. In vitro toxicity assays demonstrate that the corresponding fragment derived from recombinantly expressed human apoE is toxic to primary neurons in culture and that the E4-derived fragment is significantly more toxic than the fragment derived from the E3 isoform. These results suggest that proteolytic fragments of apoE may play a direct role in the pathology associated with AD and other diseases in which apoE has been implicated.