Genetics. Gamma-secretase and human disease.
Genetics. Gamma-secretase and human disease.
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DOI：
10.1126/science.1198668
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发表时间：
2010-11-19
期刊：
影响因子：
--
通讯作者：
Shen J
中科院分区：
文献类型：
--
作者：
Kelleher RJ 3rd;Shen J
人们怀疑阿尔茨海默病的罪魁祸首是γ-分泌酶，一种切割1型跨膜蛋白的酶。它处理淀粉样蛋白前体蛋白（APP），产生β-淀粉样蛋白（Aβ）肽，导致阿尔茨海默病患者特有的脑斑块。早老素被认为是γ-分泌酶的催化亚基，编码该亚基的psen1和psen2基因的突变是家族性阿尔茨海默病的最常见原因。在这期杂志的第1065页，Wanget等人报道了psen1的突变也与一种严重的皮肤疾病——痤疮相反——有关。编码γ-分泌酶的另外两个亚基的基因突变也与这种严重的皮肤状况有关。这一发现对γ-分泌酶在人类疾病中的功能提出了疑问，并对治疗方法的发展产生了影响。
The suspected culprit in Alzheimer's disease has been γ-secretase, an enzyme that cleaves type 1 transmembrane proteins. It processes amyloid precursor protein (APP), generating the β-amyloid (Aβ) peptides that give rise to the characteristic brain plaques of Alzheimer's disease patients. Presenilin is the presumptive catalytic subunit of γ-secretase, and mutations in thePSEN1andPSEN2genes that encode this subunit are the most common cause of familial Alzheimer's disease. On page 1065 of this issue, Wanget al.report that mutations inPSEN1are also associated with a severe skin disorder, acne inversa. Mutations in genes encoding two other subunits of γ-secretase are also linked to this severe skin condition. The finding raises questions about the function of γ-secretase in human diseases, with implications for the development of therapeutics.