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DRDs 和脑源性神经营养因子具有共同的治疗靶点:一种新的生物信息学方法为认知和行为障碍的药物治疗开辟了新的途径。

DRDs and Brain-Derived Neurotrophic Factor Share a Common Therapeutic Ground: A Novel Bioinformatic Approach Sheds New Light Toward Pharmacological Treatment of Cognitive and Behavioral Disorders.

机构信息

Department of Biotechnology, Laboratory of Genetics, School of Applied Biology and Biotechnology, Agricultural University of Athens, Athens, Greece.

University Research Institute of Maternal and Child Health & Precision Medicine, National and Kapodistrian University of Athens, "Aghia Sophia" Children's Hospital, Athens, Greece.

出版信息

Adv Exp Med Biol. 2023;1424:97-115. doi: 10.1007/978-3-031-31982-2_11.

DOI:10.1007/978-3-031-31982-2_11
PMID:37486484
Abstract

Cognitive and behavioral disorders are subgroups of mental health disorders. Both cognitive and behavioral disorders can occur in people of different ages, genders, and social backgrounds, and they can cause serious physical, mental, or social problems. The risk factors for these diseases are numerous, with a range from genetic and epigenetic factors to physical factors. In most cases, the appearance of such a disorder in an individual is a combination of his genetic profile and environmental stimuli. To date, researchers have not been able to identify the specific causes of these disorders, and as such, there is urgent need for innovative study approaches. The aim of the present study was to identify the genetic factors which seem to be more directly responsible for the occurrence of a cognitive and/or behavioral disorder. More specifically, through bioinformatics tools and software as well as analytical methods such as systemic data and text mining, semantic analysis, and scoring functions, we extracted the most relevant single nucleotide polymorphisms (SNPs) and genes connected to these disorders. All the extracted SNPs were filtered, annotated, classified, and evaluated in order to create the "genomic grammar" of these diseases. The identified SNPs guided the search for top suspected genetic factors, dopamine receptors D and neurotrophic factor BDNF, for which regulatory networks were built. The identification of the "genomic grammar" and underlying factors connected to cognitive and behavioral disorders can aid in the successful disease profiling and the establishment of novel pharmacological targets and provide the basis for personalized medicine, which takes into account the patient's genetic background as well as epigenetic factors.

摘要

认知和行为障碍是精神健康障碍的亚类。认知和行为障碍可发生在不同年龄、性别和社会背景的人群中,可导致严重的身体、心理或社会问题。这些疾病的风险因素很多,包括遗传和表观遗传因素、身体因素等。在大多数情况下,个体出现这种障碍是其遗传特征和环境刺激共同作用的结果。迄今为止,研究人员尚未能够确定这些障碍的具体原因,因此迫切需要创新的研究方法。本研究旨在确定似乎更直接导致认知和/或行为障碍发生的遗传因素。更具体地说,我们通过生物信息学工具和软件以及系统数据分析和文本挖掘、语义分析和评分功能等分析方法,提取了与这些疾病相关的最相关的单核苷酸多态性(SNP)和基因。所有提取的 SNP 都经过了过滤、注释、分类和评估,以创建这些疾病的“基因组语法”。确定的 SNP 指导了对多巴胺受体 D 和神经营养因子 BDNF 等顶级可疑遗传因素的搜索,为其构建了调控网络。确定与认知和行为障碍相关的“基因组语法”和潜在因素,可以帮助成功进行疾病特征分析,并确定新的药理学靶点,并为个体化医疗提供基础,个体化医疗考虑到了患者的遗传背景和表观遗传因素。

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