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阿尔茨海默病治疗与管理的最新进展:精准医学视角。

Recent Advances in the Treatment and Management of Alzheimer's Disease: A Precision Medicine Perspective.

机构信息

Department of Pharmacy, Guru Ghasidas Vishwavidyalaya (A Central University), Bilaspur, Chhattisgarh, India.

Department of Pharmaceutical Chemistry, ISF College of Pharmacy, Moga, Punjab, India.

出版信息

Curr Top Med Chem. 2024;24(19):1699-1737. doi: 10.2174/0115680266299847240328045737.

Abstract

About 60% to 70% of people with dementia have Alzheimer's Disease (AD), a neurodegenerative illness. One reason for this disorder is the misfolding of naturally occurring proteins in the human brain, specifically β-amyloid (Aβ) and tau. Certain diagnostic imaging techniques, such as amyloid PET imaging, tau PET imaging, Magnetic Resonance Imaging (MRI), Computerized Tomography (CT), and others, can detect biomarkers in blood, plasma, and cerebral spinal fluids, like an increased level of β-amyloid, plaques, and tangles. In order to create new pharmacotherapeutics for Alzheimer's disease, researchers must have a thorough and detailed knowledge of amyloid beta misfolding and other related aspects. Donepezil, rivastigmine, galantamine, and other acetylcholinesterase inhibitors are among the medications now used to treat Alzheimer's disease. Another medication that can temporarily alleviate dementia symptoms is memantine, which blocks the N-methyl-D-aspartate (NMDA) receptor. However, it is not able to halt or reverse the progression of the disease. Medication now on the market can only halt its advancement, not reverse it. Interventions to alleviate behavioral and psychological symptoms, exhibit anti- neuroinflammation and anti-tau effects, induce neurotransmitter alteration and cognitive enhancement, and provide other targets have recently been developed. For some Alzheimer's patients, the FDA-approved monoclonal antibody, aducanumab, is an option; for others, phase 3 clinical studies are underway for drugs, like lecanemab and donanemab, which have demonstrated potential in eliminating amyloid protein. However, additional study is required to identify and address these limitations in order to reduce the likelihood of side effects and maximize the therapeutic efficacy.

摘要

约 60%至 70%的痴呆症患者患有阿尔茨海默病(AD),这是一种神经退行性疾病。这种疾病的一个原因是人类大脑中天然存在的蛋白质错误折叠,特别是β-淀粉样蛋白(Aβ)和 tau。某些诊断成像技术,如淀粉样蛋白 PET 成像、tau PET 成像、磁共振成像(MRI)、计算机断层扫描(CT)和其他技术,可以检测血液、血浆和脑脊液中的生物标志物,如β-淀粉样蛋白水平升高、斑块和缠结。为了开发治疗阿尔茨海默病的新药物疗法,研究人员必须对淀粉样蛋白β错误折叠和其他相关方面有透彻和详细的了解。多奈哌齐、利斯的明、加兰他敏和其他乙酰胆碱酯酶抑制剂是目前用于治疗阿尔茨海默病的药物之一。另一种可以暂时缓解痴呆症状的药物是美金刚,它可以阻断 N-甲基-D-天冬氨酸(NMDA)受体。然而,它不能阻止或逆转疾病的进展。目前市场上的药物只能阻止其进展,而不能逆转。最近已经开发出了缓解行为和心理症状、表现出抗神经炎症和抗 tau 作用、诱导神经递质改变和认知增强以及提供其他靶点的干预措施。对于一些阿尔茨海默病患者,FDA 批准的单克隆抗体 aducanumab 是一种选择;对于其他患者,正在进行 lecanemab 和 donanemab 等药物的 3 期临床试验,这些药物在清除淀粉样蛋白方面显示出了潜力。然而,需要进一步研究以识别和解决这些局限性,以降低副作用的可能性并最大限度地提高治疗效果。

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