Kumar Sonu, Cieplak Piotr
SBP Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA.
SBP Medical Discovery Institute, 10901 North Torrey Pines Road, La Jolla, CA 92037, USA
Database (Oxford). 2016 Dec 26;2016. doi: 10.1093/database/baw142. Print 2016.
A variety of neurodegenerative diseases (NDs) have been associated with deregulated caspase activation that leads to neuronal death. Caspases appear to be involved in the molecular pathology of NDs by directly cleaving important proteins. For instance, several proteins involved in Alzheimer's disease, including β-amyloid precursor protein (APP) and presenilins, are known to be cleaved by caspases. Therefore, cell death pathway may play a central role in many neurological diseases, and targeting the important proteins that control the cell survival and death may potentially represent a therapeutic approach for chronic neurodegenerative disorders.
We developed CaspNeuroD, a relational database of in silico predicted caspase cleavage sites in human proteins associated with NDs. The prediction has been done on collection of 249 human proteins reported in clinical studies of NDs using the recently published CaspDB Random Forest machine-learning model. This database could be used for identifying new caspase substrates and further our understanding of the caspase-mediated substrate cleavage in NDs.
Our database provides information about potential caspase cleavage sites in a verified set of human proteins involved in NDs. It provides also information about the conservation of cleavage positions in corresponding orthologs, and information about the positions of single nucleotide polymorphisms and posttranslational modifications (PTMs) that may modulate the caspase cleavage efficiency.Database URL: caspdb.sanfordburnham.org/caspneurod.php.
多种神经退行性疾病（NDs）与半胱天冬酶激活失调有关，这会导致神经元死亡。半胱天冬酶似乎通过直接切割重要蛋白质而参与神经退行性疾病的分子病理学过程。例如，已知参与阿尔茨海默病的几种蛋白质，包括β-淀粉样前体蛋白（APP）和早老素，会被半胱天冬酶切割。因此，细胞死亡途径可能在许多神经疾病中起核心作用，针对控制细胞存活和死亡的重要蛋白质可能代表一种治疗慢性神经退行性疾病的方法。
我们开发了CaspNeuroD，这是一个关于与神经退行性疾病相关的人类蛋白质中计算机预测的半胱天冬酶切割位点的关系数据库。使用最近发表的CaspDB随机森林机器学习模型，对神经退行性疾病临床研究中报告的249种人类蛋白质进行了预测。该数据库可用于识别新的半胱天冬酶底物，并加深我们对神经退行性疾病中半胱天冬酶介导的底物切割的理解。
我们的数据库提供了一组经过验证的与神经退行性疾病相关的人类蛋白质中潜在半胱天冬酶切割位点的信息。它还提供了相应直系同源物中切割位置保守性的信息，以及可能调节半胱天冬酶切割效率的单核苷酸多态性和翻译后修饰（PTM）位置的信息。数据库网址：caspdb.sanfordburnham.org/caspneurod.php。
