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计算建模与生物标志物研究在阿尔茨海默病药物治疗中的应用(综述)。

Computational modeling and biomarker studies of pharmacological treatment of Alzheimer's disease (Review).

机构信息

Department of Biology, College of Natural Sciences, Kongju National University, Gongju, Chungcheongnam 32588, Republic of Korea.

Department of Physiology, University of Sindh, Jamshoro 76080, Pakistan.

出版信息

Mol Med Rep. 2018 Jul;18(1):639-655. doi: 10.3892/mmr.2018.9044. Epub 2018 May 22.

Abstract

Alzheimer's disease (AD) is a complex and multifactorial disease. In order to understand the genetic influence in the progression of AD, and to identify novel pharmaceutical agents and their associated targets, the present study discusses computational modeling and biomarker evaluation approaches. Based on mechanistic signaling pathway approaches, various computational models, including biochemical and morphological models, are discussed to explore the strategies that may be used to target AD treatment. Different biomarkers are interpreted on the basis of morphological and functional features of amyloid β plaques and unstable microtubule‑associated tau protein, which is involved in neurodegeneration. Furthermore, imaging and cerebrospinal fluids are also considered to be key methods in the identification of novel markers for AD. In conclusion, the present study reviews various biochemical and morphological computational models and biomarkers to interpret novel targets and agonists for the treatment of AD. This review also highlights several therapeutic targets and their associated signaling pathways in AD, which may have potential to be used in the development of novel pharmacological agents for the treatment of patients with AD. Computational modeling approaches may aid the quest for the development of AD treatments with enhanced therapeutic efficacy and reduced toxicity.

摘要

阿尔茨海默病(AD)是一种复杂的多因素疾病。为了了解 AD 进展过程中的遗传影响,并确定新的药物制剂及其相关靶点,本研究讨论了计算建模和生物标志物评估方法。基于机制信号通路方法,讨论了各种计算模型,包括生化和形态模型,以探索可能用于 AD 治疗的靶向策略。不同的生物标志物基于淀粉样β斑块和不稳定的微管相关 tau 蛋白的形态和功能特征进行解释,后者与神经退行性变有关。此外,影像学和脑脊液也被认为是识别 AD 新型标志物的关键方法。总之,本研究综述了各种生化和形态计算模型和生物标志物,以解释 AD 治疗的新型靶点和激动剂。本综述还强调了 AD 中的几个治疗靶点及其相关信号通路,这些靶点可能有潜力用于开发治疗 AD 患者的新型药物制剂。计算建模方法可能有助于寻找具有增强治疗效果和降低毒性的 AD 治疗方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4f47/6059694/38f7787ff74b/MMR-18-01-0639-g00.jpg

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