一項(xiàng)新的研究顯示,，自閉癥患者腦中的分子通路與脆性X綜合癥、安格曼綜合癥及瑞特綜合征等相關(guān)疾病密切相關(guān)而且共有某些關(guān)鍵性的蛋白質(zhì),。這些發(fā)現(xiàn)也許能夠作為發(fā)現(xiàn)更多的自閉癥基因的一個(gè)平臺(tái),。典型的自閉癥是以三個(gè)主要的特點(diǎn)作為特征的：語言及溝通能力的喪失、社交行為能力受損及重復(fù)性的動(dòng)作,。在相關(guān)的或稱癥候群性的自閉癥中，這些特征是一個(gè)大得多的癥狀組群的一部份,。癥候群性自閉癥常?？杀蛔匪葜烈粋€(gè)單一的基因，但研究人員一直難以查明經(jīng)典自閉癥的遺傳學(xué)基礎(chǔ),。
為了找到作為經(jīng)典自閉癥和癥候群性自閉癥共同基礎(chǔ)的共有的分子通路,，Huda Zogbhi及其同事應(yīng)用編碼人類蛋白質(zhì)的DNA序列庫繪制了數(shù)千個(gè)蛋白-蛋白間的相互作用圖。用已知的自閉癥相關(guān)性蛋白作為釣餌,，研究人員在DNA庫中進(jìn)行垂釣以吸引其伙伴蛋白,。他們發(fā)現(xiàn)了大約500種與自閉癥相關(guān)性蛋白有相互作用的蛋白質(zhì)。換言之,，研究人員顯示,，所有自身與自閉癥有關(guān)聯(lián)的蛋白都會(huì)通過共有伙伴蛋白而以某種方式聯(lián)系在一起。該研究團(tuán)隊(duì)的蛋白-蛋白相互作用圖凸顯了非常緊密地連接的蛋白質(zhì),；例如那些已知的在脆性X綜合癥中發(fā)生突變的蛋白,。他們的相互作用圖還顯示，2種與經(jīng)典自閉癥相關(guān)的蛋白（SHANK3 和 TSC1）會(huì)發(fā)生相互作用并共有21個(gè)共同的伙伴蛋白,。這一新的作用圖是朝著揭示可作為藥物標(biāo)靶以治療數(shù)種不同形式自閉癥的通路所邁出的早期的一步,。（生物谷Bioon.com）
生物谷推薦原文出處：
Science Translational Medicine DOI： 10.1126/scitranslmed.3002166
Protein Interactome Reveals Converging Molecular Pathways Among Autism Disorders
Sakai, Yasunari; Shaw, Chad A.; Dawson, Brian C.; Dugas, Diana V.; Al-Mohtaseb, Zaina; Hill, David E.; Zoghbi, Huda Y.
To uncover shared pathogenic mechanisms among the highly heterogeneous autism spectrum disorders (ASDs), we developed a proteininteraction network that identified hundreds of new interactions among proteins encoded by ASD-associated genes. We discoveredunexpectedly high connectivity between SHANK and TSC1, previously implicated in syndromic autism, suggesting that common molecularpathways underlie autistic phenotypes in distinct syndromes. ASD patients were more likely to harbor copy number variationsthat encompass network genes than were control subjects. We also identified, in patients with idiopathic ASD, three de novolesions (deletions in 16q23.3 and 15q22 and one duplication in Xq28) that involve three network genes (NECAB2, PKM2, and FLNA). The protein interaction network thus provides a framework for identifying causes of idiopathic autism and for understandingmolecular pathways that underpin both syndromic and idiopathic ASDs.
