Sunny Rathee, Debasis Sen, Vishal Pandey, Sanjay K Jain
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引用次数: 0
摘要
阿尔茨海默病(AD)是一种使人衰弱的神经退行性疾病,其特征是存在淀粉样蛋白-β(Aβ)斑块和含 tau 的神经纤维缠结,从而导致认知能力和身体机能下降。在大多数痴呆症病例中,注意力缺失症给全球医疗系统造成了沉重负担,发病年龄通常在 65 岁以后。虽然大多数病例都是散发性的,但约有10%的病例表现为与特定基因突变相关的常染色体形式。由折叠错误的 tau 蛋白和 Aβ 肽形成的神经纤维缠结和 Aβ 斑块会导致神经元损伤和认知障碍。目前,乙酰胆碱酯酶抑制剂和N-甲基D-天冬氨酸受体激动剂等已获批准的药物只能缓解部分症状,而不会改变疾病的进展。莱卡单抗(一种人源化 IgG1 单克隆抗体)是一种前景看好的免疫疗法。来卡尼单抗对多态 Aβ 变体具有选择性,能与大的可溶性 Aβ 聚集体结合,为靶向治疗提供了潜在的途径。人们对适应性免疫反应在AD发病机制中作用的认识发生了转变,这为旨在解决该疾病复杂机制的治疗干预措施提供了新的可能性。本综述旨在总结最近在理解阿尔茨海默病病理和创新治疗方法方面取得的进展,为研究人员和临床医生提供有价值的见解。
Advances in Understanding and Managing Alzheimer's Disease: From Pathophysiology to Innovative Therapeutic Strategies.
Alzheimer's disease (AD) is a debilitating neurodegenerative disorder characterized by the presence of amyloid-β (Aβ) plaques and tau-containing neurofibrillary tangles, leading to cognitive and physical decline. Representing the majority of dementia cases, AD poses a significant burden on healthcare systems globally, with onset typically occurring after the age of 65. While most cases are sporadic, about 10% exhibit autosomal forms associated with specific gene mutations. Neurofibrillary tangles and Aβ plaques formed by misfolded tau proteins and Aβ peptides contribute to neuronal damage and cognitive impairment. Currently, approved drugs, such as acetylcholinesterase inhibitors and N-methyl D-aspartate receptor agonists, offer only partial symptomatic relief without altering disease progression. A promising development is using lecanemab, a humanized IgG1 monoclonal antibody, as an immune therapeutic approach. Lecanemab demonstrates selectivity for polymorphic Aβ variants and binds to large soluble Aβ aggregates, providing a potential avenue for targeted treatment. This shift in understanding the role of the adaptive immune response in AD pathogenesis opens new possibilities for therapeutic interventions aiming to address the disease's intricate mechanisms. This review aims to summarize recent advancements in understanding Alzheimer's disease pathophysiology and innovative therapeutic approaches, providing valuable insights for both researchers and clinicians.
期刊介绍:
Current Drug Targets aims to cover the latest and most outstanding developments on the medicinal chemistry and pharmacology of molecular drug targets e.g. disease specific proteins, receptors, enzymes, genes.
Current Drug Targets publishes guest edited thematic issues written by leaders in the field covering a range of current topics of drug targets. The journal also accepts for publication mini- & full-length review articles and drug clinical trial studies.
As the discovery, identification, characterization and validation of novel human drug targets for drug discovery continues to grow; this journal is essential reading for all pharmaceutical scientists involved in drug discovery and development.