据一项新的研究披露，一种罕见皮肤病的基因突变让人们对一种信号转导通路有了新的了解，该通路是阿兹海默病的一个药物标靶。 反常性痤疮是毛囊的一种慢性炎症性疾病，其关键性的特征包括引流窦道、痛性皮肤脓肿及破相疤痕。 文章的作者在本期的Brevium中说，德国哲学家Karl Marx被认为就患有这种皮肤病。 为了研究这种疾病的基础遗传机制，Baoxi Wang及其同事分析了6个有反常性痤疮特征的汉人家庭成员的基因组序列。 他们发现了看来会通过令一种叫做伽马-分泌酶减活而引起该疾病的数个突变基因。人们已知这些伽马-分泌酶基因中的2个基因的突变会引起一种早发型的阿兹海默病及非阿兹海默型痴呆症。
令人感兴趣的是，对罹患反常性痤疮患者的初步分析没有发现阿兹海默病的迹象。 如果进一步的研究证明了这些突变是通过不同的机制引起这两种疾病，这将对伽马分泌酶在阿兹海默病中的作用机制及阿兹海默病的治疗药物应该如何以这种酶为标靶具有重要的意义。
生物谷推荐英文摘要：
Science DOI: 10.1126/science.1196284
gamma-Secretase Gene Mutations in Familial Acne Inversa
Baoxi Wang,1,* Wei Yang,2,* Wen Wen,3,* Jing Sun,2,* Bin Su,1,* Bo Liu,4 Donglai Ma,1 Dan Lv,2 Yaran Wen,2 Tao Qu,1 Min Chen,5 Miao Sun,2 Yan Shen,2, Xue Zhang2,3,
Acne inversa (AI), also known as hidradenitis suppurativa, is a chronic, recurrent, inflammatory disease of hair follicles that often runs in the family. We studied six Chinese families with features of AI as well as additional skin lesions on back, face, nape, and waist, and found independent loss-of-function mutations in PSENEN, PSEN1, or NCSTN, the genes encoding essential components of the -secretase multiprotein complex. Our results identify the -secretase component genes as the culprits for a subset of familial AI, implicate the -secretase-Notch pathway in the molecular pathogenesis of AI, and demonstrate that familial AI can be an allelic disorder of early-onset familial Alzheimer's disease.
1 Peking Union Medical College Hospital, Chinese Academy of Medical Sciences " Peking Union Medical College (CAMS " PUMC), Beijing, China.
2 State Key Laboratory of Medical Molecular Biology, Institute of Basic Medical Sciences, CAMS " PUMC, Beijing, China.
3 China Medical University, Shenyang, China.
4 Chinese National Human Genome Center at Beijing, Beijing, China
5 Institute of Dermatology, CAMS " PUMC, Nanjing, China.
