Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, 420 Delaware St. SE, MMC 392, Minneapolis, MN 55455, USA.
Neuropharmacology. 2013 May;68:122-35. doi: 10.1016/j.neuropharm.2012.08.015. Epub 2012 Sep 7.
Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adulthood (maintenance of synaptic function). A number of neuropsychiatric disorders including autism, schizophrenia, bipolar disorder, major depression, Alzheimer's disease and lissencephaly share a common feature of abnormal Reelin expression in the brain. Altered Reelin expression has been hypothesized to impair neuronal connectivity and synaptic plasticity, leading ultimately to the cognitive deficits present in these disorders. The mechanisms for abnormal Reelin expression in some of these disorders are currently unknown although possible explanations include early developmental insults, mutations, hypermethylation of the promoter for the Reelin gene (RELN), miRNA silencing of Reelin mRNA, FMRP underexpression and Reelin processing abnormalities. Increasing Reelin expression through pharmacological therapies may help ameliorate symptoms resulting from Reelin deficits. This article is part of the Special Issue entitled 'Neurodevelopmental Disorders'.
瑞林是一种糖蛋白，在发育过程中（调节神经元迁移和大脑分层）和成年期（维持突触功能）都发挥着重要作用。包括自闭症、精神分裂症、双相情感障碍、重度抑郁症、阿尔茨海默病和无脑回畸形在内的许多神经精神疾病的一个共同特征是大脑中瑞林表达异常。据推测，瑞林表达的改变会损害神经元的连接和突触可塑性，最终导致这些疾病中存在的认知缺陷。虽然目前尚不清楚这些疾病中某些瑞林表达异常的机制，但可能的解释包括早期发育损伤、突变、瑞林基因（RELN）启动子的高甲基化、瑞林 mRNA 的 miRNA 沉默、FMRP 表达不足和瑞林加工异常。通过药理学治疗增加瑞林的表达可能有助于改善因瑞林缺乏而导致的症状。本文是“神经发育障碍”特刊的一部分。
