Integrin adhesion in brain assembly: From molecular structure to neuropsychiatric disorders,European Journal of Neuroscience

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Integrin adhesion in brain assembly: From molecular structure to neuropsychiatric disorders
European Journal of Neuroscience ( IF 2.7 ) Pub Date : 2020-06-12 , DOI: 10.1111/ejn.14859
Fanny Jaudon _{1,

2} , Agnes Thalhammer _{1,

2} , Lorenzo A. Cingolani _{1,

3}

Affiliation

Integrins are extracellular matrix receptors that mediate biochemical and mechanical bi-directional signals between the extracellular and intracellular environment of a cell thanks to allosteric conformational changes. In the brain, they are found in both neurons and glial cells, where they play essential roles in several aspects of brain development and function, such as cell migration, axon guidance, synaptogenesis, synaptic plasticity and neuro-inflammation. Although there are many successful examples of how regulating integrin adhesion and signaling can be used for therapeutic purposes, for example for halting tumor progression, this is not the case for the brain, where the growing evidence of the importance of integrins for brain pathophysiology has not translated yet into medical applications. Here, we review recent literature showing how alterations in integrin structure, expression and signaling may be involved in the etiology of autism spectrum disorder, epilepsy, schizophrenia, addiction, depression and Alzheimer's disease. We focus on common mechanisms and recurrent signaling pathways, trying to bridge studies on the genetics and molecular structure of integrins with those on synaptic physiology and brain pathology. Further, we discuss integrin-targeting strategies and their potential benefits for therapeutic purposes in neuropsychiatric disorders.

中文翻译：

大脑组装中的整合素粘附：从分子结构到神经精神疾病

由于变构构象变化，整联蛋白是细胞外基质受体，可在细胞的细胞外和细胞内环境之间介导生化和机械双向信号。在大脑中，它们存在于神经元和神经胶质细胞中，它们在大脑发育和功能的多个方面发挥重要作用，例如细胞迁移、轴突引导、突触发生、突触可塑性和神经炎症。尽管有许多成功的例子说明如何将整合素粘附和信号传导用于治疗目的，例如用于阻止肿瘤进展，但对于大脑而言情况并非如此，越来越多的证据表明整合素对脑病理生理学的重要性尚未尚未转化为医疗应用。这里，我们回顾了最近的文献，这些文献表明整合素结构、表达和信号传导的改变可能与自闭症谱系障碍、癫痫、精神分裂症、成瘾、抑郁和阿尔茨海默病的病因有关。我们专注于常见机制和循环信号通路，试图将整合素的遗传学和分子结构的研究与突触生理学和脑病理学的研究联系起来。此外，我们讨论了整合素靶向策略及其对神经精神疾病治疗目的的潜在益处。试图将整合素的遗传学和分子结构的研究与突触生理学和脑病理学的研究联系起来。此外，我们讨论了整合素靶向策略及其对神经精神疾病治疗目的的潜在益处。试图将整合素的遗传学和分子结构的研究与突触生理学和脑病理学的研究联系起来。此外，我们讨论了整合素靶向策略及其对神经精神疾病治疗目的的潜在益处。

更新日期：2020-06-12

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