Department of Pharmaceutical Science, School of Pharmacy, Bharat Institute of Technology (BIT), Meerut 250103, UP, India.
Department of Pharmacology, National Institute of Pharmaceutical Education and Research (NIPER), S.A.S. Nagar, Punjab 160062, India.
Curr Med Chem. 2024;31(31):5004-5026. doi: 10.2174/0929867331666230727103553.
Alzheimer's disease (AD) is a complex neurological disorder that results in cognitive decline. The incidence rates of AD have been increasing, particularly among individuals 60 years of age or older. In June 2021, the US FDA approved aducanumab, the first humanized monoclonal antibody, as a potential therapeutic option for AD. Clinical trials have shown this drug to effectively target the accumulation of Aβ (beta-amyloid) plaques in the brain, and its effectiveness is dependent on the dosage and duration of treatment. Additionally, aducanumab has been associated with improvements in cognitive function. Biogen, the pharmaceutical company responsible for developing and marketing aducanumab, has positioned it as a potential breakthrough for treating cerebral damage in AD. However, the drug has raised concerns due to its high cost, limitations, and potential side effects. AD is a progressive neurological condition that affects memory, cognitive function, and behaviour. It significantly impacts the quality of life of patients and caregivers and strains healthcare systems. Ongoing research focuses on developing disease-modifying therapies that can halt or slow down AD progression. The pathogenesis of AD involves various molecular cascades and signaling pathways. However, the formation of extracellular amyloid plaques is considered a critical mechanism driving the development and progression of the disease. Aducanumab, as a monoclonal antibody, has shown promising results in inhibiting amyloid plaque formation, which is the primary pathological feature of AD. This review explores the signaling pathways and molecular mechanisms through which aducanumab effectively prevents disease pathogenesis in AD.
阿尔茨海默病(AD)是一种复杂的神经退行性疾病,可导致认知能力下降。AD 的发病率一直在上升,尤其是在 60 岁或以上的人群中。2021 年 6 月,美国 FDA 批准 aducanumab 作为 AD 的潜在治疗选择,这是首个人类单克隆抗体。临床试验表明,该药物能有效靶向大脑中 Aβ(β-淀粉样蛋白)斑块的积累,其疗效取决于治疗的剂量和持续时间。此外,aducanumab 与认知功能的改善有关。开发和销售 aducanumab 的制药公司 Biogen 将其定位为治疗 AD 脑损伤的潜在突破。然而,由于其高成本、局限性和潜在的副作用,该药物引起了人们的关注。AD 是一种进行性神经疾病,会影响记忆、认知功能和行为。它会显著影响患者和护理人员的生活质量,并给医疗保健系统带来压力。目前的研究重点是开发能够阻止或减缓 AD 进展的疾病修饰疗法。AD 的发病机制涉及多种分子级联和信号通路。然而,细胞外淀粉样斑块的形成被认为是驱动疾病发展和进展的关键机制。作为一种单克隆抗体,aducanumab 已显示出抑制淀粉样斑块形成的良好效果,淀粉样斑块形成是 AD 的主要病理特征。本综述探讨了 aducanumab 有效预防 AD 发病机制的信号通路和分子机制。