據(jù)一項(xiàng)新的研究披露,，一種罕見(jiàn)皮膚病的基因突變讓人們對(duì)一種信號(hào)轉(zhuǎn)導(dǎo)通路有了新的了解，該通路是阿茲海默病的一個(gè)藥物標(biāo)靶,。 反常性痤瘡是毛囊的一種慢性炎癥性疾病,，其關(guān)鍵性的特征包括引流竇道、痛性皮膚膿腫及破相疤痕,。 文章的作者在本期的Brevium中說(shuō),，德國(guó)哲學(xué)家Karl Marx被認(rèn)為就患有這種皮膚病。 為了研究這種疾病的基礎(chǔ)遺傳機(jī)制,，Baoxi Wang及其同事分析了6個(gè)有反常性痤瘡特征的漢人家庭成員的基因組序列,。 他們發(fā)現(xiàn)了看來(lái)會(huì)通過(guò)令一種叫做伽馬-分泌酶減活而引起該疾病的數(shù)個(gè)突變基因。人們已知這些伽馬-分泌酶基因中的2個(gè)基因的突變會(huì)引起一種早發(fā)型的阿茲海默病及非阿茲海默型癡呆癥,。
令人感興趣的是,，對(duì)罹患反常性痤瘡患者的初步分析沒(méi)有發(fā)現(xiàn)阿茲海默病的跡象。 如果進(jìn)一步的研究證明了這些突變是通過(guò)不同的機(jī)制引起這兩種疾病,，這將對(duì)伽馬分泌酶在阿茲海默病中的作用機(jī)制及阿茲海默病的治療藥物應(yīng)該如何以這種酶為標(biāo)靶具有重要的意義。（生物谷Bioon.com）
生物谷推薦英文摘要：
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.
