Presenilins as therapeutic targets for the treatment of Alzheimer's disease

被引:42
作者
Golde, TE [1 ]
Younkin, SG [1 ]
机构
[1] Mayo Clin Jacksonville, Dept Neurosci, Jacksonville, FL 32224 USA
关键词
D O I
10.1016/S1471-4914(01)02064-0
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Studies demonstrating that accumulation and aggregation of the amyloid beta protein (A beta) within the brain is likely to cause Alzheimer's disease (AD) have provided the rationale for therapeutic strategies aimed at influencing A beta production, aggregation and clearance. gamma -secretase catalyzes the final cleavage that releases the A beta from its precursor; therefore, it is a potential therapeutic target for the treatment of AD. Recent data show that the polytopic membrane proteins presenilin 1 and presenilin 2 are either catalytic components or essential co-factors of a membrane-bound proteolytic complex that possesses gamma -secretase activity, Although recent findings demonstrating that gamma -secretase inhibitors bind directly to presenilins (PSs) further support a catalytic role for PSs in gamma -secretase cleavage, additional studies ate still needed to clarify the role of PSs in gamma -secretase cleavage and the use of targeting PSs to reduce A beta production.
引用
收藏
页码:264 / 269
页数:6
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