ADNP 在自噬中发挥关键作用:从自闭症到精神分裂症和阿尔茨海默病。

ADNP Plays a Key Role in Autophagy: From Autism to Schizophrenia and Alzheimer's Disease.

机构信息

The Lily and Avraham Gildor Chair for the Investigation of Growth Factors The Elton Laboratory for Neuroendocrinology Department of Human Molecular Genetics and Biochemistry, Sackler Faculty of Medicine, Sagol School of Neuroscience and Adams Super Center for Brain Studies, Tel Aviv University, Tel Aviv 69978, Israel.

出版信息

Bioessays. 2017 Nov;39(11). doi: 10.1002/bies.201700054. Epub 2017 Sep 21.

Abstract

Activity-dependent neuroprotective protein (ADNP), discovered in our laboratory in 1999, has been characterized as a master gene vital for mammalian brain formation. ADNP de novo mutations in humans result in a syndromic form of autism-like spectrum disorder (ASD), including cognitive and motor deficits, the ADNP syndrome (Helsmoortel-Van Der Aa). One of the most important cellular processes associated with ADNP is the autophagy pathway, recently discovered by us as a key player in the pathophysiology of schizophrenia. In this regard, given the link between the microtubule and autophagy systems, the ADNP microtubule end binding protein motif, namely, the neuroprotective NAP (NAPVSIPQ), was found to enhance autophagy while protecting microtubules and augmenting ADNP's association with both systems. Thus, linking autophagy and ADNP is proposed as a major target for intervention in brain diseases from autism to Alzheimer's disease (AD) and our findings introduce autophagy as a possible novel target for treating schizophrenia.

摘要

活性依赖型神经保护蛋白(ADNP)于 1999 年在我们的实验室中被发现,其被描述为对哺乳动物大脑形成至关重要的主基因。人类 ADNP 的从头突变导致类似自闭症的综合征形式的自闭症谱系障碍(ASD),包括认知和运动缺陷,ADNP 综合征(Helsmoortel-Van Der Aa)。与 ADNP 相关的最重要的细胞过程之一是自噬途径,最近我们发现它是精神分裂症病理生理学的关键参与者。在这方面,鉴于微管和自噬系统之间的联系,ADNP 的微管末端结合蛋白基序,即神经保护 NAP(NAPVSIPQ),被发现增强自噬,同时保护微管并增加 ADNP 与两个系统的关联。因此,将自噬与 ADNP 联系起来被提议作为干预从自闭症到阿尔茨海默病(AD)等脑部疾病的主要靶点,我们的发现将自噬引入为治疗精神分裂症的可能新靶点。

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索