Mackie Shaun, Millar J Kirsty, Porteous David J
Medical Genetics Section, University of Edinburgh Centre for Molecular Medicine, Western General Hospital, Crewe Road, Edinburgh, EH4 2XU, UK.
Curr Opin Neurobiol. 2007 Feb;17(1):95-102. doi: 10.1016/j.conb.2007.01.007. Epub 2007 Jan 26.
How can we hope to explain mechanistically the schizophrenic phenotype? Perhaps through the reductionist approach of genetics, which is beginning to yield biological clues. Growing evidence supports the view that the well-established genetic risk factor DISC1 plays an important role in schizophrenia biology by interacting with FEZ1 and NDEL1 during neurodevelopment and with the phosphodiesterase PDE4B in neuronal cell signalling. Thus, DISC1 and its pathways support the neurodevelopmental hypothesis of schizophrenia and provide a mechanistic explanation for the characteristic cognitive deficits. Genetic variants of DISC1 also predispose to related affective (mood) disorders. As a consequence, we can speculate on the mechanisms of DISC1 action and possible routes to treatment for these common, debilitating brain disorders.
我们如何有望从机制上解释精神分裂症的表型呢？或许可以通过遗传学的还原论方法，这种方法已开始提供生物学线索。越来越多的证据支持这样一种观点，即已得到充分证实的遗传风险因素DISC1在精神分裂症生物学中发挥重要作用，它在神经发育过程中与FEZ1和NDEL1相互作用，并在神经元细胞信号传导中与磷酸二酯酶PDE4B相互作用。因此，DISC1及其通路支持精神分裂症的神经发育假说，并为其典型的认知缺陷提供了一种机制性解释。DISC1的基因变异也易引发相关的情感（情绪）障碍。因此，我们可以推测DISC1的作用机制以及针对这些常见的、使人衰弱的脑部疾病可能的治疗途径。
