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Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology 精神分裂症背外侧前额叶皮质 AKT-mTOR 信号通路蛋白下调。

影响因子：8.294 DOI：10.1038/s41386-020-0614-2

作者： Chadha R,Meador-Woodruff JH 发表时间：2020-02-03 03:20:47

from：《NEUROPSYCHOPHARMACOLOGY》

keywords： Chadha RMeador-Woodruff JH

关键词：

Abstract

:Abnormal neurotransmission is central to schizophrenia (SZ). Alterations across multiple neurotransmitter systems in SZ suggest that this illness may be associated with dysregulation of core intracellular processes such as signaling pathways that underlie the regulation and integration of these systems. The AKT-mTOR signaling cascade has been implicated in SZ by gene association, postmortem brain and animal studies. AKT and mTOR are serine/threonine kinases which play important roles in cell growth, proliferation, survival, and differentiation. Both AKT and mTOR require phosphorylation at specific sites for their complete activation. mTOR forms two functionally distinct multiprotein complexes, mTOR Complex 1 (mTORC1) and Complex 2 (mTORC2). mTORC1 mediates ribosome biogenesis, protein translation, and autophagy, whereas mTORC2 contributes to actin dynamics. Altered protein synthesis and actin dynamics can lead to an abnormal neuronal morphology resulting in deficits in learning and memory. Currently, there is a lack of direct evidence to support the hypothesis of disrupted mTOR signaling in SZ, and we have addressed this by characterizing this signaling pathway in SZ brain. We found a reduction in AKT and mTOR protein expression and/or phosphorylation state in dorsolateral prefrontal cortex (DLPFC) from 22 pairs of SZ and matched comparison subjects. We also found reduced protein expression of GβL, a subunit protein common to both mTOR complexes. We further investigated mTOR complex-specific subunit composition and phosphorylation state, and found abnormal mTOR expression in both complexes in SZ DLPFC. These findings provide evidence that proteins associated with the AKT-mTOR signaling cascade are downregulated in SZ DLPFC.

摘要

: 异常神经传递是精神分裂症 (SZ) 的核心。SZ 中多种神经递质系统的改变表明，这种疾病可能与核心细胞内过程的失调有关，如作为这些系统调控和整合基础的信号通路。通过基因关联、死后大脑和动物研究，AKT-mTOR 信号级联与 SZ 有关。AKT 和 mTOR 是丝氨酸/苏氨酸激酶，在细胞生长、增殖、存活和分化中起重要作用。AKT 和 mTOR 都需要在特定位点磷酸化才能完全激活。MTOR 形成两个功能不同的多蛋白复合物，mTOR 复合物 1 (mTORC1) 和复合物 2 (mTORC2)。mTORC1 介导核糖体生物合成、蛋白翻译和自噬，而 mTORC2 有助于肌动蛋白动力学。改变蛋白质合成和肌动蛋白动力学可导致神经元形态异常，导致学习和记忆缺陷。目前，缺乏直接证据支持 SZ 中 mTOR 信号被破坏的假设，我们通过表征 SZ 大脑中的这一信号通路来解决这一问题。我们从 22 对 SZ 和匹配的比较受试者中发现背外侧前额叶皮质 (DLPFC) 中 AKT 和 mTOR 蛋白表达和/或磷酸化状态减少。我们还发现 g β l 的蛋白表达减少，g β l 是两种 mTOR 复合物共同的亚基蛋白。我们进一步研究了 mTOR 复合物特异性亚基组成和磷酸化状态，发现 SZ DLPFC 中两种复合物中 mTOR 表达异常。这些发现提供了与 AKT-mTOR 信号级联相关的蛋白在 SZ DLPFC 中下调的证据。

期刊介绍

《NEUROPSYCHOPHARMACOLOGY》 (点击进入期刊详情)

英文简介 : Neuropsychopharmacology is an international scientific journal and the official publication of the American College of Neuropsychopharmacology (ACNP). This journal focuses upon the clinical and basic science contributions that advance our understanding of the brain and behavior, especially as related to the molecular, cellular, physiological and psychological properties of agents acting within the central nervous system and the identification of new molecular targets for the development of the next generations of psychotropic drugs. While original reports are preferred, minireviews and perspectives are invited by the editorial office. In view of the interdisciplinary nature of the field, particular emphasis is placed on studies that address the biological substrates of normal and pathological behavior, the nature, etiology and pathophysiology of neuropsychiatric disorders, biologically relevant aspects of the epidemeology, diagnosis, and treatment of these disorders, and the basic mechanisms by which psychopharmacological agents exert their effect.

中文简介 : （来自Google、百度翻译）《神经精神药理学》是一份国际科学期刊，也是美国神经精神药理学学院(ACNP)的官方出版物。这个杂志主要集中在临床和基础科学的贡献,促进我们的大脑和行为的理解,特别是相关的分子、细胞、生理和心理的属性代理代理在中枢神经系统和新的分子靶点的识别发展的精神药品的下一代。编辑部欢迎原创报道，也欢迎评论和观点。针对该领域的跨学科性质,特别强调研究解决正常和病理行为反应的生理机制,自然,神经精神障碍的病因和病理生理学,生物epidemeology有关方面,诊断和治疗这些疾病,和精神药理学的基本机制发挥他们的作用。

CIRCULATION RESEARCH 期刊中科院评价数据

新中科院分区

大类(学科)	小类(学科)	学科排名
医学	NEUROSCIENCES (神经科学) PHARMACOLOGY & PHARMACY (药学) PSYCHIATRY (精神病学)	21/261 13/261 10/142

大类(学科)

小类(学科)

学科排名

医学

NEUROSCIENCES (神经科学)

PHARMACOLOGY & PHARMACY (药学)

PSYCHIATRY (精神病学)

21/261
13/261
10/142

新发布的期刊年发文量

年度总发文量	年度论文发表量	年度综述发表量
235	208	27

总被引频次 :25672

特征因子 : 0.039090

影响因子趋势图

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