阿尔茨海默病治疗面临的挑战:针对显著病理因素的药物治疗的最新进展和策略。
Challenges in the treatment of Alzheimer's disease: recent progress and treatment strategies of pharmaceuticals targeting notable pathological factors.
机构信息
a Department of Chemical Engineering , National Chung Cheng University , Chia-Yi , Taiwan , Republic of China.
出版信息
Expert Rev Neurother. 2019 Jul;19(7):623-652. doi: 10.1080/14737175.2019.1621750. Epub 2019 May 29.
: Alzheimer's disease (AD), a commonly encountered neurodegenerative disorder, causes cognitive decline and has a devastating effect on the quality of life. AD occurs mainly through abnormal amyloid β peptide (Aβ) and tau protein (tau) activity around/in neurons. Aβ-based therapeutic techniques have been struggled to treat AD over the past few decades. In addition, the complexity in treating AD is due to diverse factors regulating its pathology. : This review emphasizes recent advances regarding various pathological approaches and provides an overview of the most recent medications for AD. The authors focus on the regulatory factors, which mediate AD pathology, and discuss a variety of newly developed drugs and compounds used to inhibit β-secretase and γ-secretase activity, remove oligomeric Aβ and aggregated Aβ that is given responsibility in the amyloid cascade hypothesis, prevent tau hyperphosphorylation, restrain phosphorylated tau (p-tau) aggregation, remove aggregated p-tau that is proposed in tauopathy, and other related pathways. : The approaches to the treatment of AD towards Aβ and tau have failed in most clinical attempts due to insufficient disease models arising from complex AD biology. It is the time to look for other approaches and pathological factors to cure AD.
阿尔茨海默病(AD)是一种常见的神经退行性疾病,可导致认知能力下降,并对生活质量造成严重影响。AD 的发生主要与神经元周围/内异常的淀粉样β肽(Aβ)和 tau 蛋白(tau)的活性有关。在过去的几十年中,基于 Aβ 的治疗技术一直在努力治疗 AD。此外,AD 治疗的复杂性还在于调节其病理的多种因素。
本文重点介绍了各种病理方法的最新进展,并概述了 AD 的最新药物。作者关注调节 AD 病理的调控因子,并讨论了多种新开发的药物和化合物,这些药物和化合物用于抑制β-分泌酶和γ-分泌酶活性、去除寡聚 Aβ 和在淀粉样蛋白级联假说中负责的聚集 Aβ、预防 tau 过度磷酸化、抑制磷酸化 tau(p-tau)聚集、去除在 tau 病中提出的聚集 p-tau,以及其他相关途径。
由于 AD 生物学的复杂性导致疾病模型不足,AD 针对 Aβ 和 tau 的治疗方法在大多数临床尝试中都失败了。现在是时候寻找其他方法和病理因素来治疗 AD 了。