Suppr超能文献

阿尔茨海默病诊断与治疗干预的当前进展、挑战及未来前景

Current progress, challenges and future prospects of diagnostic and therapeutic interventions in Alzheimer's disease.

作者信息

Rajasekhar K, Govindaraju Thimmaiah

机构信息

Bioorganic Chemistry Laboratory, New Chemistry Unit, Jawaharlal Nehru Centre for Advanced Scientific Research (JNCASR) Jakkur P.O. Bengaluru 560064 Karnataka India

出版信息

RSC Adv. 2018 Jun 29;8(42):23780-23804. doi: 10.1039/c8ra03620a. eCollection 2018 Jun 27.

Abstract

Alzheimer's disease (AD) is the most prevalent, progressive and multifaceted neurodegenerative disorder associated with cognition, memory and behavioural impairments. There is no approved diagnosis or cure for AD, and it affects both developed and developing countries and causes a significant social and economic burden. Extracellular senile plaques of amyloid beta (Aβ) and intracellular neurofibrillary tangles of phosphorylated Tau (pTau) in the brain are considered to be the pathophysiological hallmarks of AD. In an attempt to explain the complexity and multifactorial nature of AD, various hypotheses (Aβ aggregation, Tau aggregation, metal dyshomeostasis, oxidative stress, cholinergic dysfunction, inflammation and downregulation of autophagy) based on pathophysiological changes that occur during the onset and progression of AD have been proposed. However, none of the hypotheses is capable of independently explaining the pathological conditions observed in AD. The complex and multifaceted pathophysiological nature of AD has hampered the identification and validation of effective biomarkers for early diagnosis and the development of disease-modifying therapies. Nevertheless, the amyloid hypothesis is the most widely accepted and is closely correlated with disease symptoms of AD that encompass all the disease hypotheses. Therefore, amyloid plaques are ideal biomarkers for the development of an early diagnosis of AD. Similarly, the formation of amyloid plaques can also serve as a target for the design of therapeutic tools an inclusive approach that considers multiple disease pathways involved in AD. Our review article briefly introduces pathophysiological factors involved in AD using interdependent but diverse hypotheses. Recent advances in the development of effective molecular tools and techniques for diagnostic and therapeutic interventions in AD, especially those in the advanced stages (clinical trials) of development, are given special consideration. In addition, contributions from our laboratory to the development of selective molecular tools for diagnostic and therapeutic interventions that target multifaceted toxicity in AD are also covered. In summary, we discuss diverse aspects of molecular mechanisms that underlie the pathogenesis of multifactorial AD, current progress and possible bottlenecks that have hampered the development of early diagnostic tools and effective drugs. Challenges and future prospects include the integration of various disease pathways for the successful development of an early diagnosis and effective drugs for the treatment of AD.

摘要

阿尔茨海默病(AD)是最常见、渐进性且多方面的神经退行性疾病,与认知、记忆和行为障碍相关。目前尚无获批的AD诊断方法或治愈手段,它在发达国家和发展中国家均有影响,并造成了巨大的社会和经济负担。大脑中细胞外的β淀粉样蛋白(Aβ)老年斑和细胞内磷酸化Tau蛋白(pTau)神经原纤维缠结被认为是AD的病理生理特征。为了解释AD的复杂性和多因素性质,基于AD发病和进展过程中发生的病理生理变化,人们提出了各种假说(Aβ聚集、Tau聚集、金属离子稳态失衡、氧化应激、胆碱能功能障碍、炎症和自噬下调)。然而,没有一种假说能够独立解释AD中观察到的病理状况。AD复杂多面的病理生理性质阻碍了用于早期诊断的有效生物标志物的识别和验证以及疾病修饰疗法的开发。尽管如此,淀粉样蛋白假说被广泛接受,并且与涵盖所有疾病假说的AD疾病症状密切相关。因此,淀粉样蛋白斑是AD早期诊断开发的理想生物标志物。同样,淀粉样蛋白斑的形成也可作为治疗工具设计的靶点——这是一种考虑到AD中多种疾病途径的综合方法。我们的综述文章使用相互依存但多样的假说简要介绍了AD涉及的病理生理因素。特别考虑了用于AD诊断和治疗干预的有效分子工具和技术开发的最新进展,尤其是那些处于开发后期(临床试验)的进展。此外,还涵盖了我们实验室对针对AD多方面毒性的诊断和治疗干预选择性分子工具开发的贡献。总之,我们讨论了多因素AD发病机制背后分子机制的不同方面、当前进展以及阻碍早期诊断工具和有效药物开发的可能瓶颈。挑战和未来前景包括整合各种疾病途径以成功开发AD的早期诊断方法和有效治疗药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d7f5/9081849/f34dfe97fedc/c8ra03620a-f1.jpg

文献AI研究员

20分钟写一篇综述,助力文献阅读效率提升50倍。

立即体验

用中文搜PubMed

大模型驱动的PubMed中文搜索引擎

马上搜索

文档翻译

学术文献翻译模型,支持多种主流文档格式。

立即体验