Gozes Illana
Lily and Avraham Gildor Chair for the Investigation of Growth Factors; 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, Israel.
J Neurosci Res. 2017 Jan 2;95(1-2):652-660. doi: 10.1002/jnr.23808.
Discovered in our laboratory, activity-dependent neuroprotective protein (ADNP) interacts with key regulatory proteins, including the chromatin remodeling complex SWI/SNF, proteins associated with RNA splicing, RNA translation, microtubule dynamics, and autophagy. ADNP regulates > 400 genes during mouse embryonic development and is essential for neural tube closure. ADNP key functions extend from mice to men, with mutations causing ADNP-related ID/autism syndrome, also known as the Helsmoortel-Van der Aa syndrome. ADNP mRNA increases in lymphocytes derived from schizophrenia patients and in patients suffering from mild cognitive impairment (MCI) and further increases in Alzheimer's disease patients compared with controls. Serum ADNP levels correlate with IQ. NAP (davunetide), an ADNP snippet drug candidate, protects cognition in patients suffering from amnestic MCI preceding Alzheimer's disease and significantly enhances functional daily activities in schizophrenia patients toward future development. It is important to note that ADNP is sexually regulated in the brains of birds, mice, and men and in lymphocytes of patients suffering from schizophrenia. ADNP haploinsufficiency in mice results in significantly decreased axonal transport (with male-female differences) changes in gene expression in a sex-dependent manner, including key regulatory mechanisms during brain and heart development and function and behavioral outcomes. These findings pave the path for better understanding of brain function through the prism of sex differences. © 2016 Wiley Periodicals, Inc.
活性依赖的神经保护蛋白（ADNP）是在我们实验室发现的，它与关键调节蛋白相互作用，包括染色质重塑复合体SWI/SNF、与RNA剪接、RNA翻译、微管动力学和自噬相关的蛋白。在小鼠胚胎发育过程中，ADNP调节超过400个基因，对神经管闭合至关重要。ADNP的关键功能从小鼠扩展到人类，其突变会导致ADNP相关的智力障碍/自闭症综合征，也称为赫尔斯莫尔特 - 范德阿综合征。与对照组相比，精神分裂症患者、轻度认知障碍（MCI）患者以及阿尔茨海默病患者淋巴细胞中的ADNP mRNA水平升高。血清ADNP水平与智商相关。NAP（达武奈肽）是一种ADNP片段候选药物，可保护早发性阿尔茨海默病遗忘型MCI患者的认知功能，并显著增强精神分裂症患者的日常功能活动，具有未来开发潜力。需要注意的是，ADNP在鸟类、小鼠和人类大脑以及精神分裂症患者的淋巴细胞中存在性别调控。小鼠中的ADNP单倍剂量不足会导致轴突运输显著减少（存在性别差异），基因表达也会以性别依赖的方式发生变化，包括大脑和心脏发育、功能及行为结果中的关键调控机制。这些发现为通过性别差异的视角更好地理解脑功能铺平了道路。© 2016威利期刊公司
