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针对阿尔茨海默病中β淀粉样蛋白和tau 病的最新治疗策略。

Recent therapeutic strategies targeting beta amyloid and tauopathies in Alzheimer's disease.

机构信息

Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L.Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India.

Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKMs NMIMS, V.L.Mehta Road, Vile Parle (W), Mumbai, Maharashtra, 400056, India.

出版信息

Brain Res Bull. 2019 Mar;146:171-184. doi: 10.1016/j.brainresbull.2019.01.004. Epub 2019 Jan 8.

Abstract

Alzheimer's disease (AD) has been a global concern for years due to its severe implications that affects the quality of life of the patients. The available line of therapy for treating Alzheimer's includes acetylcholinesterase inhibitors, NMDA(N-methyl-D-aspartate) antagonists and their combination which gives only symptomatic relief rather than treating the root cause of AD. Senile plaques and neurofibrillary tangles are the characteristic features underlying Alzheimer's pathology. Several attempts have been made towards exploring the niceties of these hallmarks and targeting various aspects of amyloid and tau pathology at different stages to eliminate the ultimate cause. Approaches targeting cleavage and formation of toxic amyloid fragments by secretases, aggregation of amyloid monofilaments, and immunotherapy against amyloid deposits has been extensively studied to treat amyloid pathology. Similarly, for tau pathology, tau hyperphosphorylation, microtubule stabilization, anti-tau immunotherapy has been explored. This article focuses on AD pathology and current pharmacotherapy, precisely for amyloid and tau. Furthermore, preclinical and clinical studies along with potential leads discovered under these approaches have also been included in this article. However, despite extensive research in drug development, overcoming clinical barrier still remain a major challenge for Alzheimer's pharmacotherapy.

摘要

阿尔茨海默病(AD)多年来一直是全球关注的焦点,因为它严重影响了患者的生活质量。目前用于治疗阿尔茨海默病的治疗方法包括乙酰胆碱酯酶抑制剂、NMDA(N-甲基-D-天冬氨酸)拮抗剂及其联合应用,这些方法只能提供症状缓解,而不能治疗 AD 的根本原因。老年斑和神经原纤维缠结是阿尔茨海默病病理学的特征。人们已经进行了多次尝试,探索这些标志物的细微差别,并针对淀粉样蛋白和 tau 病理学的各个方面在不同阶段进行靶向治疗,以消除最终原因。针对通过分泌酶切割和形成有毒淀粉样片段、淀粉样单丝聚集以及针对淀粉样沉积物的免疫疗法的方法已经得到了广泛研究,以治疗淀粉样蛋白病理学。同样,对于 tau 病理学,已经探索了 tau 过度磷酸化、微管稳定、抗 tau 免疫疗法。本文重点介绍 AD 病理学和当前的药物治疗,特别是针对淀粉样蛋白和 tau。此外,还包括这些方法下的临床前和临床研究以及发现的潜在靶点。然而,尽管在药物开发方面进行了广泛的研究,克服临床障碍仍然是阿尔茨海默病药物治疗的主要挑战。

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