精神分裂症（schizophrenia）是一组病因未明的精神疾病，具有思维、情感、行为等多方面的障碍，以精神活动和环境不协调为特征。许多名人都罹患有精神分裂症，比如诺贝尔奖得主约翰奈许（电影《美丽心灵》原型），林肯的妻子玛丽托德林肯等。在中国，成年人口中的终生患病率为1%左右。1993年全国流调资料显示精神分裂症的终生患病率为6.55‰，患病率均与家庭经济水平呈负相关。我国目前有近600万人罹患精神分裂症。
DISC蛋白是精神分裂症和其他情绪障碍的一个重要风险因子，其编码基因：disc1能编码一种在成熟大脑中充当新生神经细胞的一类“音乐指挥棒（musical conductor）”，指导新细胞达到适当的位置，以使它们能够完美地整合进我们复杂的神经系统中。如果DISC1蛋白不能正常工作，那么新的神经元就会无法融入神经系统“大家庭”。
在最新研究中，研究人员证明抑制DISC蛋白的表达会导致神经祖细胞增生减少，从而引起过早的细胞周期完结和分化。这种功能是通过GSK3β/β-catenin途径，原因有两个，第一个是DISC1能通过直接物理作用，抑制GSK3β活性，其次，GSK3抑制子能帮助祖细胞正常增殖，以及逆转由于DISC遗失导致的行为缺陷。因此研究人员认为这说明这种蛋白能通过GSK3β/β-catenin途径调控胚胎和成人神经祖细胞增殖，这为disc1这种易感基因如何导致精神分裂症提出了新观点。
之前的一些研究暗示，DISC1对神经迁移和延伸很重要，而这项对小鼠的新研究则揭示出这种蛋白质比之前推测的更为关键，并且可能揭示出DISC1为何与多种精神疾病有关。（生物谷Bioon.com）
生物谷推荐原始出处：
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.
