精神分裂癥（schizophrenia）是一組病因未明的精神疾病,，具有思維,、情感、行為等多方面的障礙,，以精神活動(dòng)和環(huán)境不協(xié)調(diào)為特征,。許多名人都罹患有精神分裂癥，比如諾貝爾獎(jiǎng)得主約翰奈許（電影《美麗心靈》原型）,，林肯的妻子瑪麗托德林肯等,。在中國,，成年人口中的終生患病率為1%左右。1993年全國流調(diào)資料顯示精神分裂癥的終生患病率為6.55‰,，患病率均與家庭經(jīng)濟(jì)水平呈負(fù)相關(guān),。我國目前有近600萬人罹患精神分裂癥。
DISC蛋白是精神分裂癥和其他情緒障礙的一個(gè)重要風(fēng)險(xiǎn)因子,，其編碼基因：disc1能編碼一種在成熟大腦中充當(dāng)新生神經(jīng)細(xì)胞的一類“音樂指揮棒（musical conductor）”,，指導(dǎo)新細(xì)胞達(dá)到適當(dāng)?shù)奈恢茫允顾鼈兡軌蛲昝赖卣线M(jìn)我們復(fù)雜的神經(jīng)系統(tǒng)中,。如果DISC1蛋白不能正常工作,，那么新的神經(jīng)元就會無法融入神經(jīng)系統(tǒng)“大家庭”。
在最新研究中,，研究人員證明抑制DISC蛋白的表達(dá)會導(dǎo)致神經(jīng)祖細(xì)胞增生減少,，從而引起過早的細(xì)胞周期完結(jié)和分化。這種功能是通過GSK3β/β-catenin途徑,，原因有兩個(gè),，第一個(gè)是DISC1能通過直接物理作用，抑制GSK3β活性,，其次,，GSK3抑制子能幫助祖細(xì)胞正常增殖，以及逆轉(zhuǎn)由于DISC遺失導(dǎo)致的行為缺陷,。因此研究人員認(rèn)為這說明這種蛋白能通過GSK3β/β-catenin途徑調(diào)控胚胎和成人神經(jīng)祖細(xì)胞增殖,，這為disc1這種易感基因如何導(dǎo)致精神分裂癥提出了新觀點(diǎn)。
之前的一些研究暗示,，DISC1對神經(jīng)遷移和延伸很重要,，而這項(xiàng)對小鼠的新研究則揭示出這種蛋白質(zhì)比之前推測的更為關(guān)鍵，并且可能揭示出DISC1為何與多種精神疾病有關(guān),。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell, 20 March 2009 doi:10.1016/j.cell.2008.12.044
Disrupted in Schizophrenia 1 Regulates Neuronal Progenitor Proliferation via Modulation of GSK3 β/β-Catenin Signaling
Yingwei Mao1,2,Xuecai Ge1,2,3,Christopher L. Frank1,2,Jon M. Madison7,Angela N. Koehler6,Mary Kathryn Doud6,Carlos Tassa6,Erin M. Berry6,7,Takahiro Soda1,2,4,5,Karun K. Singh1,2,Travis Biechele1,8,9,Tracey L. Petryshen6,7,Randall T. Moon1,8,9,Stephen J. Haggarty6,7andLi-Huei Tsai1,2,7,,
1 Howard Hughes Medical Institute, Cambridge, MA 02139, USA
2 Picower Institute for Learning and Memory, Department of Brain and Cognitive Sciences, Massachusetts Institute of Technology, Cambridge, MA 02139, USA
3 Program in Neuroscience, Harvard Medical School, Boston, MA 02115, USA
4 M.D.-Ph.D. program, Harvard Medical School, Boston, MA 02115, USA
5 Harvard-MIT Division of Health Sciences and Technology, Harvard Medical School, Boston, MA 02115, USA
6 Psychiatric and Neurodevelopmental Genetics Unit and Molecular Neurogenetics Unit, Center for Human Genetic Research, Massachusetts General Hospital, Boston, MA 02114, USA
7 Stanley Center for Psychiatric Research, Broad Institute of Harvard and Massachusetts Institute of Technology, Cambridge, MA 02139, USA
8 Department of Pharmacology, University of Washington School of Medicine, Seattle, WA 98195, USA
9 Institute for Stem Cell and Regenerative Medicine, University of Washington School of Medicine, Seattle, WA 98195, USA
Summary
The Disrupted in Schizophrenia 1 (DISC1) gene is disrupted by a balanced chromosomal translocation (1;11) (q42; q14.3) in a Scottish family with a high incidence of major depression, schizophrenia, and bipolar disorder. Subsequent studies provided indications that DISC1 plays a role in brain development. Here, we demonstrate that suppression of DISC1 expression reduces neural progenitor proliferation, leading to premature cell cycle exit and differentiation. Several lines of evidence suggest that DISC1 mediates this function by regulating GSK3. First, DISC1 inhibits GSK3 activity through direct physical interaction, which reduces -catenin phosphorylation and stabilizes β-catenin. Importantly, expression of stabilized -catenin overrides the impairment of progenitor proliferation caused by DISC1 loss of function. Furthermore, GSK3 inhibitors normalize progenitor proliferation and behavioral defects caused by DISC1 loss of function. Together, these results implicate DISC1 in GSK3 β/β-catenin signaling pathways and provide a framework for understanding how alterations in this pathway may contribute to the etiology of psychiatric disorders.
