Mohammad Umar , Yasir Rehman , Subiya Ambreen , Sayed Md Mumtaz , Mohd Shaququzzaman , Mohammad Mumtaz Alam , Ruhi Ali
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引用次数: 0
Abstract
Alzheimer's disease (AD) presents a complex pathology involving amyloidogenic proteolysis, neuroinflammation, mitochondrial dysfunction, and cholinergic deficits. Oxidative stress exacerbates AD progression through pathways like macromolecular peroxidation, mitochondrial dysfunction, and metal ion redox potential alteration linked to amyloid-beta (Aβ). Despite limited approved medications, heterocyclic compounds have emerged as promising candidates in AD drug discovery. This review highlights recent advancements in synthetic heterocyclic compounds targeting oxidative stress, mitochondrial dysfunction, and neuroinflammation in AD. Additionally, it explores the potential of nanomaterial-based drug delivery systems to overcome challenges in AD treatment. Nanoparticles with heterocyclic scaffolds, like polysorbate 80-coated PLGA and Resveratrol-loaded nano-selenium, show improved brain transport and efficacy. Micellar CAPE and Melatonin-loaded nano-capsules exhibit enhanced antioxidant properties, while a tetra hydroacridine derivative (CHDA) combined with nano-radiogold particles demonstrates promising acetylcholinesterase inhibition without toxicity. This comprehensive review underscores the potential of nanotechnology-driven drug delivery for optimizing the therapeutic outcomes of novel synthetic heterocyclic compounds in AD management. Furthermore, the inclusion of various promising heterocyclic compounds with detailed ADMET (Absorption, Distribution, Metabolism, Excretion, and Toxicity) data provides valuable insights for planning the development of novel drug delivery treatments for AD.
阿尔茨海默病(AD)病理复杂,涉及淀粉样蛋白酶解、神经炎症、线粒体功能障碍和胆碱能障碍。氧化应激通过大分子过氧化、线粒体功能障碍以及与淀粉样β(Aβ)相关的金属离子氧化还原电位改变等途径,加剧了阿兹海默症的进展。尽管已批准的药物有限,但杂环化合物已成为发现抗多发性硬化症药物的有希望的候选药物。本综述重点介绍了针对氧化应激、线粒体功能障碍和神经炎症的合成杂环化合物的最新进展。此外,它还探讨了基于纳米材料的给药系统在克服 AD 治疗难题方面的潜力。具有杂环支架的纳米颗粒,如聚苯乙酸酯 80 涂层聚乳酸乙烯雌酚(PLGA)和负载白藜芦醇的纳米硒,显示出更好的脑转运和疗效。微胶囊 CAPE 和褪黑素纳米胶囊显示出更强的抗氧化性,而四氢吖啶衍生物(CHDA)与纳米放射金颗粒的结合则显示出无毒的乙酰胆碱酯酶抑制作用。这篇综合性综述强调了纳米技术驱动的药物输送在优化新型合成杂环化合物在治疗注意力缺失症方面的治疗效果的潜力。此外,该综述还收录了各种有前景的杂环化合物,并提供了详细的 ADMET(吸收、分布、代谢、排泄和毒性)数据,为规划新型 AD 药物递送疗法的开发提供了宝贵的见解。
期刊介绍:
With the rise in average human life expectancy, the impact of ageing and age-related diseases on our society has become increasingly significant. Ageing research is now a focal point for numerous laboratories, encompassing leaders in genetics, molecular and cellular biology, biochemistry, and behavior. Ageing Research Reviews (ARR) serves as a cornerstone in this field, addressing emerging trends.
ARR aims to fill a substantial gap by providing critical reviews and viewpoints on evolving discoveries concerning the mechanisms of ageing and age-related diseases. The rapid progress in understanding the mechanisms controlling cellular proliferation, differentiation, and survival is unveiling new insights into the regulation of ageing. From telomerase to stem cells, and from energy to oxyradical metabolism, we are witnessing an exciting era in the multidisciplinary field of ageing research.
The journal explores the cellular and molecular foundations of interventions that extend lifespan, such as caloric restriction. It identifies the underpinnings of manipulations that extend lifespan, shedding light on novel approaches for preventing age-related diseases. ARR publishes articles on focused topics selected from the expansive field of ageing research, with a particular emphasis on the cellular and molecular mechanisms of the aging process. This includes age-related diseases like cancer, cardiovascular disease, diabetes, and neurodegenerative disorders. The journal also covers applications of basic ageing research to lifespan extension and disease prevention, offering a comprehensive platform for advancing our understanding of this critical field.