Négyessy László, Györffy Balázs, Hanics János, Bányai Mihály, Fonta Caroline, Bazsó Fülöp
Theoretical Neuroscience and Complex Systems Research Group, Wigner Research Center for Physics, Budapest, Hungary,
Subcell Biochem. 2015;76:185-205. doi: 10.1007/978-94-017-7197-9_10.
Despite the growing body of evidence pointing on the involvement of tissue non-specific alkaline phosphatase (TNAP) in brain function and diseases like epilepsy and Alzheimer's disease, our understanding about the role of TNAP in the regulation of neurotransmission is severely limited. The aim of our study was to integrate the fragmented knowledge into a comprehensive view regarding neuronal functions of TNAP using objective tools. As a model we used the signal transduction molecular network of a pyramidal neuron after complementing with TNAP related data and performed the analysis using graph theoretic tools. The analyses show that TNAP is in the crossroad of numerous pathways and therefore is one of the key players of the neuronal signal transduction network. Through many of its connections, most notably with molecules of the purinergic system, TNAP serves as a controller by funnelling signal flow towards a subset of molecules. TNAP also appears as the source of signal to be spread via interactions with molecules involved among others in neurodegeneration. Cluster analyses identified TNAP as part of the second messenger signalling cascade. However, TNAP also forms connections with other functional groups involved in neuronal signal transduction. The results indicate the distinct ways of involvement of TNAP in multiple neuronal functions and diseases.
尽管越来越多的证据表明组织非特异性碱性磷酸酶（TNAP）参与脑功能以及癫痫和阿尔茨海默病等疾病，但我们对TNAP在神经传递调节中的作用的了解仍然极为有限。我们研究的目的是使用客观工具将零散的知识整合为关于TNAP神经元功能的全面观点。作为模型，我们在补充TNAP相关数据后使用锥体神经元的信号转导分子网络，并使用图论工具进行分析。分析表明，TNAP处于众多通路的交叉点，因此是神经元信号转导网络的关键参与者之一。通过其许多连接，最显著的是与嘌呤能系统的分子连接，TNAP通过将信号流导向分子子集而充当控制器。TNAP还似乎是通过与神经退行性变等过程中涉及的分子相互作用而传播的信号源。聚类分析将TNAP确定为第二信使信号级联的一部分。然而，TNAP也与参与神经元信号转导的其他功能组形成连接。结果表明TNAP以不同方式参与多种神经元功能和疾病。
