Sharma Saurabh, Rahate Kalpana, Kumar Rahul
Department of Pharmacy, School of Medical and Allied Sciences, Galgotias University, Greater Noida, Uttar Pradesh, 203201, India.
Cent Nerv Syst Agents Med Chem. 2024 Oct 21. doi: 10.2174/0118715249333381241012073557.
The accumulation of tau-containing neurofibrillary tangles and beta-amyloid deposits has been identified as the hallmark of Alzheimer's disease. Alzheimer's disease (AD) is a hereditary and neurological condition that can result in non-amnestic cognitive decline in less common forms and amnestic memory loss in its classic form. While Alzheimer's disease is the most prevalent cause of memory loss in middle-aged and older adults, other neurodegenerative and cerebrovascular disorders can have an impact on the disease's clinical course. Designing multi-target-directed ligands (MTDLs) is a very promising modern approach. This methodology was designed specifically for treating disorders with complex pathological mechanisms. Among these disorders is Alzheimer's disease (AD), which is currently the most prevalent multifactorial neurodegenerative illness. Increased amounts of the amyloid βpeptide (Aβ) and hyperphosphorylated tau protein, together with the loss of neurons and synapses, are linked to Alzheimer's disease (AD). Additionally, there is evidence that the pathophysiology of this condition is influenced by oxidative stress, metal ion dysregulation, inflammation, and failure of the cell cycle regulatory system. Since Alzheimer's disease (AD) is a multi-factor illness, there are many attractive targets for the development of anti-AD medications. These molecules can be useful in treating AD since they are multi-target-directed. This review focuses on the discovery of dual and multi-acting anti-AD drug candidates, especially hybrids made by combining chemically active moieties that function against distinct targets. The first group of substances consists of cholinesterase inhibitors with extra properties or those that function as multiple binding site inhibitors. Natural products also provide numerous options for slowing the progression and symptoms of many diseases, including Alzheimer's Meanwhile, Natural chemical structures with the following characteristics: alkaloids, sterols, triterpenes, tannins, flavonoids, polyphenols, and antioxidants as well as anti-inflammatory and anti-amyloidogenic properties. We provide an overview of Alzheimer's disease pathophysiology and therapy targets in this study. We also show several isolated chemicals and medicinal plants that are used to treat and prevent the symptoms of Alzheimer's disease.
含tau蛋白的神经原纤维缠结和β-淀粉样蛋白沉积的积累已被确定为阿尔茨海默病的标志。阿尔茨海默病（AD）是一种遗传性神经疾病，较少见的形式可导致非遗忘性认知衰退，典型形式则导致遗忘性记忆丧失。虽然阿尔茨海默病是中老年人群记忆力丧失的最常见原因，但其他神经退行性疾病和脑血管疾病也会影响该疾病的临床病程。设计多靶点导向配体（MTDLs）是一种非常有前景的现代方法。该方法是专门为治疗具有复杂病理机制的疾病而设计的。这些疾病中包括阿尔茨海默病（AD），它是目前最常见的多因素神经退行性疾病。淀粉样β肽（Aβ）和过度磷酸化的tau蛋白含量增加，以及神经元和突触的丧失，都与阿尔茨海默病（AD）有关。此外，有证据表明，这种疾病的病理生理学受到氧化应激、金属离子失调、炎症和细胞周期调节系统功能障碍的影响。由于阿尔茨海默病（AD）是一种多因素疾病，因此抗AD药物的开发有许多有吸引力的靶点。这些分子具有多靶点导向作用，可用于治疗AD。本综述重点关注双效和多效抗AD候选药物的发现，特别是通过结合针对不同靶点起作用的化学活性部分制成的杂合物。第一类物质包括具有额外特性的胆碱酯酶抑制剂或作为多结合位点抑制剂起作用的物质。天然产物也为减缓包括阿尔茨海默病在内的许多疾病的进展和症状提供了众多选择。同时，具有以下特征的天然化学结构：生物碱、甾醇、三萜、单宁、黄酮类、多酚和抗氧化剂，以及抗炎和抗淀粉样生成特性。在本研究中，我们概述了阿尔茨海默病的病理生理学和治疗靶点。我们还展示了几种用于治疗和预防阿尔茨海默病症状的分离化学物质和药用植物。
