The involvement of Reelin in neurodevelopmental disorders.

The involvement of Reelin in neurodevelopmental disorders.
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DOI:
10.1016/j.neuropharm.2012.08.015
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发表时间:
2013-05
期刊:
影响因子:
4.7
通讯作者:
Fatemi SH
Fatemi SH
中科院分区:
医学2区
文献类型:
--
作者:
Folsom TD;Fatemi SH

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Reelin是一种糖蛋白,在发育(调节神经元迁移和脑分层)和成人(维持突触功能)中发挥重要作用。包括自闭症、精神分裂症、双相情感障碍、重性抑郁症、阿尔茨海默病和无脑回畸形在内的许多神经精神障碍都有一个共同的特征,即大脑中的Reelin表达异常。已经假设改变的Reelin表达损害神经元连接和突触可塑性,最终导致这些疾病中存在的认知缺陷。目前尚不清楚这些疾病中的一些疾病中的异常Reelin表达的机制,尽管可能的解释包括早期发育损伤、突变、Reelin基因(Reelin gene)启动子的超甲基化、Reelin mRNA的miRNA沉默和Reelin加工异常。通过药物治疗增加Reelin表达可能有助于改善由Reelin缺陷引起的症状。
Reelin is a glycoprotein that serves important roles both during development (regulation of neuronal migration and brain lamination) and in adults (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 is currently unknown although possible explanations include early developmental insults, mutations, hypermethylation of the promoter for the Reelin gene (RELN), miRNA silencing of Reelin mRNA, and Reelin processing abnormalities. Increasing Reelin expression through pharmacological therapies may help ameliorate symptoms resulting from Reelin deficits.
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