{"title":"Novel Emerging Targets Identification in Reducing Risk of Alzheimer's Disease.","authors":"Saurabh Sharma, Kalpana Rahate, Rahul Kumar","doi":"10.2174/0118715249333381241012073557","DOIUrl":null,"url":null,"abstract":"<p><p>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.</p>","PeriodicalId":93930,"journal":{"name":"Central nervous system agents in medicinal chemistry","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2024-10-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Central nervous system agents in medicinal chemistry","FirstCategoryId":"1085","ListUrlMain":"https://doi.org/10.2174/0118715249333381241012073557","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
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 的神经纤维缠结和 beta 淀粉样蛋白沉积物的积累已被确定为阿尔茨海默病的特征。阿尔茨海默病(AD)是一种遗传性神经系统疾病,在不常见的情况下会导致非失忆性认知能力下降,在典型的情况下会导致失忆性失忆。虽然阿尔茨海默病是中老年人记忆力减退的最主要原因,但其他神经退行性疾病和脑血管疾病也会对该病的临床过程产生影响。设计多靶点配体(MTDL)是一种非常有前景的现代方法。这种方法专为治疗病理机制复杂的疾病而设计。其中,阿尔茨海默病(AD)是目前最常见的多因素神经退行性疾病。淀粉样β肽(Aβ)和高磷酸化 tau 蛋白的增加,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失效的影响。由于阿尔茨海默病(AD)是一种多因素疾病,因此在开发抗 AD 药物方面有许多具有吸引力的靶点。由于这些分子具有多靶点导向性,因此可用于治疗阿尔茨海默病。本综述将重点讨论双效和多效抗注意力缺失症候选药物的发现,特别是通过结合针对不同靶点的化学活性分子制成的混合物。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的胆碱酯酶抑制剂。天然产品也为延缓包括阿尔茨海默氏症在内的多种疾病的进展和症状提供了多种选择 同时,天然产品的化学结构具有以下特点:生物碱、甾醇、三萜类、单宁酸、黄酮类、多酚类、抗氧化剂以及抗炎和抗淀粉样蛋白生成特性。我们在这项研究中概述了阿尔茨海默病的病理生理学和治疗目标。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。