Department of Medical Biotechnology, College of Life Science and Biotechnology, Dongguk University, Seoul 04620, Korea.
Int J Mol Sci. 2021 Feb 26;22(5):2341. doi: 10.3390/ijms22052341.
Alzheimer's disease (AD) is a neurodegenerative disease characterized by severe brain damage and dementia. There are currently few therapeutics to treat this disease, and they can only temporarily alleviate some of the symptoms. The pathogenesis of AD is mainly preceded by accumulation of abnormal amyloid beta (Aβ) aggregates, which are toxic to neurons. Therefore, modulation of the formation of these abnormal aggregates is strongly suggested as the most effective approach to treat AD. In particular, numerous studies on natural products associated with AD, aiming to downregulate Aβ peptides and suppress the formation of abnormal Aβ aggregates, thus reducing neural cell death, are being conducted. Generation of Aβ peptides can be prevented by targeting the secretases involved in Aβ-peptide formation (secretase-dependent). Additionally, blocking the intra- and intermolecular interactions of Aβ peptides can induce conformational changes in abnormal Aβ aggregates, whereby the toxicity can be ameliorated (structure-dependent). In this review, AD-associated natural products which can reduce the accumulation of Aβ peptides via secretase- or structure-dependent pathways, and the current clinical trial states of these products are discussed.
阿尔茨海默病（AD）是一种神经退行性疾病，其特征是严重的大脑损伤和痴呆。目前治疗这种疾病的方法很少，而且只能暂时缓解一些症状。AD 的发病机制主要是由异常淀粉样β（Aβ）聚集体的积累引起的，这些聚集体对神经元有毒。因此，调节这些异常聚集体的形成被强烈认为是治疗 AD 的最有效方法。特别是，正在进行大量关于与 AD 相关的天然产物的研究，旨在下调 Aβ 肽并抑制异常 Aβ 聚集体的形成，从而减少神经细胞死亡。通过针对参与 Aβ 肽形成的酶（依赖于酶的）可以防止 Aβ 肽的产生。此外，阻断 Aβ 肽的分子内和分子间相互作用可以诱导异常 Aβ 聚集体的构象变化，从而减轻毒性（依赖于结构）。在这篇综述中，讨论了可以通过依赖于酶或结构的途径减少 Aβ 肽积累的与 AD 相关的天然产物，以及这些产物的当前临床研究状态。
