Twenty-nine missense mutations linked with familial Alzheimer's disease alter the processing of presenilin 1

被引:21
作者
Murayama, O [1 ]
Murayama, M [1 ]
Honda, T [1 ]
Sun, XY [1 ]
Nihonmatsu, N [1 ]
Takashima, A [1 ]
机构
[1] RIKEN, Brain Sci Inst, Lab Alzheimers Dis, Wako, Saitama 3510198, Japan
关键词
Alzheimer's disease; missense mutation; presenilin; processing;
D O I
10.1016/S0278-5846(99)00034-2
中图分类号
R74 [神经病学与精神病学];
学科分类号
摘要
1. Full-length form of human presenilin 1 (PS 1) is processed and an N-terminal fragment (28 KD) and C-terminal fragment (19 KD) are generated. To elucidate the possible role of pnsenilin mutations in Alzheimer's disease (AD), the authors analyze the effects of AD-linked mutations on PS1 processing in cultured cells. 2. Complementary DNAs encoding genes for human PSI harboring twenty-nine missense mutations linked with familial Alzheimer's disease (FAD) were introduced into PC12 cells. Human PS1 exogenously expressed in the cells was detected by immunoblotting using a monoclonal antibody that recognized the N-terminal region of human PS1. The amounts of full-length form (48 KD) and N-terminal fragment (28 KD) of PS1 was quantified by densitometrical analysis. 3. The ratio of the N-terminal fragment to total PS1 was reduced by twenty-nine mutations. The specific effects on PS1 processing varied according to mutation. 4. These results suggest that AD-linked missense mutations of PS 1 are involved in neurodegeneration via inhibition of PS1 processing.
引用
收藏
页码:905 / 913
页数:9
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