PSD95: A synaptic protein implicated in schizophrenia or autism?
PSD95: A synaptic protein implicated in schizophrenia or autism?
复制标题
DOI：
10.1016/j.pnpbp.2017.11.016
复制
发表时间：
2018-03-02
影响因子：
5.6
通讯作者：
Gao WJ
中科院分区：
文献类型：
--
作者：
Coley AA;Gao WJ
脑兴奋性突触中突触后致密物（postsynaptic density，PSD）的分子组成是神经发育障碍如精神分裂症（schizophrenia，SCZ）和自闭症的主要病因之一。突触后密度蛋白-95（Postsynaptic density protein-95，PSD-95）是突触成熟的主要调节因子，与N-甲基-D-天冬氨酸受体（NMDARs）和α-氨基-3-羟基-5-甲基-4-异恶唑丙酸受体（AMPAR s）相互作用，稳定并运输到突触后膜。最近，有压倒性的证据表明，PSD-95中断与SCZ和自闭症中观察到的认知和学习缺陷有关。例如，最近对精神病患者的基因组和测序研究突出了包括PSD-95功能障碍在内的突触能突触PSD的畸变。在动物研究中，PSD-95缺乏显示特定脑区的NMDA和AMPA受体组成和功能的改变，这可能有助于在神经精神病理学中观察到的表型。在这篇综述中，我们描述了PSD-95作为一个重要的支架蛋白在突触和神经发育过程中的作用。更具体地说，我们讨论了它与NMDA受体亚基的相互作用，可能会影响谷氨酸的传输，并在神经发育的关键时间点形成沉默的突触。此外，我们描述了PSD-95如何改变树突棘形态，从而调节突触功能，影响SCZ与自闭症的行为表型。了解PSD-95在SCZ和自闭症的神经病理学中的作用将使我们深入了解这些疾病的细胞和分子属性，从而为受影响的患者提供治疗选择。
The molecular components of the postsynaptic density (PSD) in excitatory synapses of the brain are currently being investigated as one of the major etiologies of neurodevelopmental disorders such as schizophrenia (SCZ) and autism. Postsynaptic density protein-95 (PSD-95) is a major regulator of synaptic maturation by interacting, stabilizing and trafficking N-methyl-D-aspartic acid receptors (NMDARs) and α-amino-3-hydroxy-5- methyl-4-isox-azoleproprionic acid receptors (AMPARs) to the postsynaptic membrane. Recently, there has been overwhelming evidence that associates PSD-95 disruption with cognitive and learning deficits observed in SCZ and autism. For instance, recent genomic and sequencing studies of psychiatric patients highlight the aberrations at the PSD of glutamatergic synapses that include PSD-95 dysfunction. In animal studies, PSD-95 deficiency shows alterations in NMDA and AMPA-receptor composition and function in specific brain regions that may contribute to phenotypes observed in neuropsychiatric pathologies. In this review, we describe the role of PSD-95 as an essential scaffolding protein during synaptogenesis and neurodevelopment. More specifically, we discuss its interactions with NMDA receptor subunits that potentially affect glutamate transmission, and the formation of silent synapses during critical time points of neurodevelopment. Furthermore, we describe how PSD-95 may alter dendritic spine morphologies, thus regulating synaptic function that influences behavioral phenotypes in SCZ versus autism. Understanding the role of PSD-95 in the neuropathologies of SCZ and autism will give an insight of the cellular and molecular attributes in the disorders, thus providing treatment options in patients affected.
登录
查看更多内容
DOI：
10.2174/1874440001105010040
发表时间：
2011-01-01
期刊：
The open neuroimaging journal
影响因子：
--
作者：
Amen, Daniel G;Trujillo, Manuel;Chaitin, Barry
通讯作者：
Chaitin, Barry
影响因子：
6.2
作者：
Fujita-Jimbo E;Tanabe Y;Yu Z;Kojima K;Mori M;Li H;Iwamoto S;Yamagata T;Momoi MY;Momoi T
通讯作者：
Momoi T
影响因子：
16.2
作者：
Elias, Guillermo M.;Funke, Lars;Nicoll, Roger A.
通讯作者：
Nicoll, Roger A.
DOI：
10.1073/pnas.1517045112
发表时间：
2015-12-15
影响因子：
11.1
作者：
Chen, Xiaobing;Levy, Jonathan M.;Reese, Thomas S.
通讯作者：
Reese, Thomas S.
影响因子：
4.7
作者：
Collingridge GL;Volianskis A;Bannister N;France G;Hanna L;Mercier M;Tidball P;Fang G;Irvine MW;Costa BM;Monaghan DT;Bortolotto ZA;Molnár E;Lodge D;Jane DE
通讯作者：
Jane DE