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阿尔茨海默病治疗的近期进展综述

A Review of Recent Advances in the Management of Alzheimer's Disease.

作者信息

Thangwaritorn Skylynn, Lee Christopher, Metchikoff Elena, Razdan Vidushi, Ghafary Suliman, Rivera Dominic, Pinto Alvaro, Pemminati Sudhakar

机构信息

Department of Biomedical Education, California Health Sciences University College of Osteopathic Medicine, Clovis, USA.

出版信息

Cureus. 2024 Apr 16;16(4):e58416. doi: 10.7759/cureus.58416. eCollection 2024 Apr.

Abstract

Alzheimer's disease (AD) is the most common neurodegenerative condition and a form of dementia encountered in medical practice. Despite many proposed and attempted treatments, this disease remains a major puzzle in the public health systems worldwide. The initial part of this article provides an overview and illustration of the primary mechanisms responsible for neuronal damage in AD. Subsequently, it offers a critical evaluation of the most noteworthy studies on pharmacological therapy for AD and outlines recent advancements and novel approaches to managing this condition. Main properties, categorization, Food and Drug Administration (FDA) status, mechanisms of action, benefits, and common side effects of the classical and the most recently proposed pharmacological treatments for AD are described. The conventional pharmacological agents revised comprise cholinesterase inhibitors, monoclonal antibodies, and other therapies, such as memantine, valproic acid, and rosiglitazone. The innovative reviewed pharmacological agents comprise the monoclonal antibodies: donanemab, gantenerumab, solanezumab, bapineuzumab, crenezumab, and semorinemab. Nutritional supplements such as alpha-tocopherol (vitamin E) and caprylidene are also revised. Tau and amyloid-targeting treatments include methylthioninium moiety (MT), leuco-methylthioninium bis (LMTM), an oxidized form of MT, and tramiprosate, which inhibits the beta-amyloid (Aβ) monomer aggregation into toxic oligomers. Antidiabetic and anti-neuroinflammation drugs recently proposed for AD treatment are discussed. The antidiabetic drugs include NE3107, an anti-inflammatory and insulin sensitizer, and the diabetes mainstream drug metformin. The anti-neuroinflammatory AD therapies include the use of sodium oligomannate (GV-971), infusions with intravenous immunoglobulin aiming to decrease plasma levels of the constituents of Aβ plaques, and masitinib, a tyrosine kinase inhibitor that impacts mast and microglia cells. Additional anti-inflammatory agents being currently tested in phase-2 clinical trials, such as atomoxetine (selective norepinephrine reuptake inhibitor), losartan (angiotensin 2 receptor agonist), genistein (anti-inflammatory isoflavone neuroprotective agent), trans-resveratrol (polyphenol antioxidant plant estrogen), and benfotiamine (synthetic thiamine precursor), were reviewed. Lastly, drugs targeting Alzheimer's-associated symptoms, such as brexpiprazole (serotonin dopamine activity modulator) and suvorexant (orexin receptor antagonist), respectively, used for agitation and insomnia in AD patients, are reviewed. As experimental investigations and clinical research progress, there is a possibility that a combination of newly tested medications and traditional ones may emerge as a promising treatment option for AD in the future.

摘要

阿尔茨海默病(AD)是最常见的神经退行性疾病,也是医学实践中遇到的一种痴呆症形式。尽管提出并尝试了许多治疗方法,但这种疾病在全球公共卫生系统中仍然是一个重大难题。本文首先概述并阐述了导致AD神经元损伤的主要机制。随后,对AD药物治疗方面最值得关注的研究进行了批判性评估,并概述了管理这种疾病的最新进展和新方法。描述了AD经典和最新提出的药物治疗的主要特性、分类、美国食品药品监督管理局(FDA)的批准状态、作用机制、益处和常见副作用。所回顾的传统药物包括胆碱酯酶抑制剂、单克隆抗体以及其他疗法,如美金刚、丙戊酸和罗格列酮。所回顾的创新药物包括单克隆抗体:多奈单抗、甘特单抗、索拉单抗、巴匹兹单抗、克列奈单抗和塞莫瑞单抗。还回顾了营养补充剂,如α-生育酚(维生素E)和辛酰碘苯腈。针对tau蛋白和淀粉样蛋白的治疗方法包括亚甲蓝部分(MT)、亚甲蓝双聚体(LMTM,MT的氧化形式)以及曲美普明,后者可抑制β-淀粉样蛋白(Aβ)单体聚集成有毒寡聚体。讨论了最近提出的用于AD治疗的抗糖尿病和抗神经炎症药物。抗糖尿病药物包括具有抗炎和胰岛素增敏作用的NE3107以及糖尿病主流药物二甲双胍。抗神经炎症的AD治疗方法包括使用寡聚甘露糖酸钠(GV-971)、静脉注射免疫球蛋白以降低Aβ斑块成分的血浆水平,以及马西替尼,一种影响肥大细胞和小胶质细胞的酪氨酸激酶抑制剂。还回顾了目前正在进行2期临床试验的其他抗炎药物,如托莫西汀(选择性去甲肾上腺素再摄取抑制剂)、氯沙坦(血管紧张素2受体激动剂)、染料木黄酮(具有抗炎作用的异黄酮神经保护剂)、反式白藜芦醇(多酚抗氧化植物雌激素)和苯磷硫胺(合成硫胺素前体)。最后,回顾了针对AD相关症状的药物,如分别用于治疗AD患者激越和失眠的布雷哌唑(5-羟色胺多巴胺活性调节剂)和苏沃雷生(食欲素受体拮抗剂)。随着实验研究和临床研究的进展,未来新测试药物与传统药物的联合使用有可能成为AD有前景的治疗选择。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/054a/11098549/db6666d851ff/cureus-0016-00000058416-i01.jpg

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