Gozes Illana, Yeheskel Adva, Pasmanik-Chor Metsada
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, Israel.
The Bioinformatics Unit, George S. Wise Faculty of Life Sciences, Tel Aviv University, Tel Aviv, Israel.
J Alzheimers Dis. 2015;45(1):57-73. doi: 10.3233/JAD-142490.
The recent finding of activity-dependent neuroprotective protein (ADNP) as a protein decreased in serum of patients with Alzheimer's disease (AD) compared to controls, alongside with the discovery of ADNP mutations in autism and coupled with the original description of cancer mutations, ignited an interest for a comparative analysis of ADNP with other AD/autism/cancer-associated genes. We strive toward a better understanding of the molecular structure of key players in psychiatric/neurodegenerative diseases including autism, schizophrenia, and AD. This article includes data mining and bioinformatics analysis on the ADNP gene and protein, in addition to other related genes, with emphasis on recent literature. ADNP is discovered here as unique to chordata with specific autism mutations different from cancer-associated mutation. Furthermore, ADNP exhibits similarities to other cancer/autism-associated genes. We suggest that key genes, which shape and maintain our brain and are prone to mutations, are by in large unique to chordata. Furthermore, these brain-controlling genes, like ADNP, are linked to cell growth and differentiation, and under different stress conditions may mutate or exhibit expression changes leading to cancer propagation. Better understanding of these genes could lead to better therapeutics.
最近发现，与对照组相比，阿尔茨海默病（AD）患者血清中活性依赖神经保护蛋白（ADNP）水平降低，同时在自闭症患者中发现了ADNP突变，再加上最初对癌症突变的描述，引发了对ADNP与其他AD/自闭症/癌症相关基因进行比较分析的兴趣。我们致力于更好地理解包括自闭症、精神分裂症和AD在内的精神/神经退行性疾病关键参与者的分子结构。本文除了对其他相关基因进行数据挖掘和生物信息学分析外，还重点关注了ADNP基因和蛋白质的最新文献。在此发现ADNP是脊索动物特有的，其特定的自闭症突变不同于癌症相关突变。此外，ADNP与其他癌症/自闭症相关基因存在相似性。我们认为，塑造和维持我们大脑且易于发生突变的关键基因在很大程度上是脊索动物特有的。此外，这些控制大脑的基因，如ADNP，与细胞生长和分化相关，在不同的应激条件下可能发生突变或表现出表达变化，从而导致癌症扩散。对这些基因的更好理解可能会带来更好的治疗方法。
