The secretases: enzymes with therapeutic potential in Alzheimer disease.
The secretases: enzymes with therapeutic potential in Alzheimer disease.
复制标题
DOI：
10.1038/nrneurol.2009.218
复制
发表时间：
2010-02
影响因子：
38.1
通讯作者：
Golde, Todd
中科院分区：
文献类型：
--
作者：
De Strooper, Bart;Vassar, Robert;Golde, Todd
The amyloid hypothesis has yielded a series of well-validated candidate drug targets with potential for the treatment of Alzheimer disease (AD). Three proteases that are involved in the processing of amyloid precursor protein—α-secretase, β-secretase and γ-secretase—are of particular interest as they are central to the generation and modulation of amyloid-β peptide and can be targeted by small compounds in vitro and in vivo. Given that these proteases also fulfill other important biological roles, inhibiting their activity will clearly be inherently associated with mechanism-based toxicity. Carefully determining a suitable therapeutic window and optimizing the selectivity of the drug treatments towards amyloid precursor protein processing might be ways of overcoming this potential complication. Secretase inhibitors are likely to be the first small-molecule therapies aimed at AD modification that will be fully tested in the clinic. Success or failure of these first-generation AD therapies will have enormous consequences for further drug development efforts for AD and possibly other neurodegenerative conditions.
登录
查看更多内容
影响因子：
56.9
作者：
GOLDE, TE;ESTUS, S;YOUNKIN, SG
通讯作者：
YOUNKIN, SG
影响因子：
4.8
作者：
Buxbaum, JD;Liu, KN;Black, RA
通讯作者：
Black, RA
影响因子：
4.8
作者：
Chavez-Gutierrez, Lucia;Tolia, Alexandra;de Strooper, Bart
通讯作者：
de Strooper, Bart
影响因子：
64.8
作者：
De Strooper, B;Saftig, P;Van Leuven, F
通讯作者：
Van Leuven, F
影响因子：
4.8
作者：
Dominguez, D;Tournoy, J;De Strooper, B
通讯作者：
De Strooper, B