Salk Institute for Biological Studies, La Jolla, CA 92037, USA.
Int J Mol Sci. 2019 Jun 22;20(12):3056. doi: 10.3390/ijms20123056.
Neurodegenerative diseases, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and amyotrophic lateral sclerosis (ALS), currently affect more than 6 million people in the United States. Unfortunately, there are no treatments that slow or prevent disease development and progression. Regardless of the underlying cause of the disorder, age is the strongest risk factor for developing these maladies, suggesting that changes that occur in the aging brain put it at increased risk for neurodegenerative disease development. Moreover, since there are a number of different changes that occur in the aging brain, it is unlikely that targeting a single change is going to be effective for disease treatment. Thus, compounds that have multiple biological activities that can impact the various age-associated changes in the brain that contribute to neurodegenerative disease development and progression are needed. The plant-derived flavonoids have a wide range of activities that could make them particularly effective for blocking the age-associated toxicity pathways associated with neurodegenerative diseases. In this review, the evidence for beneficial effects of multiple flavonoids in models of AD, PD, HD, and ALS is presented and common mechanisms of action are identified. Overall, the preclinical data strongly support further investigation of specific flavonoids for the treatment of neurodegenerative diseases.
神经退行性疾病包括阿尔茨海默病(AD)、帕金森病(PD)、亨廷顿病(HD)和肌萎缩侧索硬化症(ALS),目前影响美国超过 600 万人。不幸的是,目前还没有能够减缓或阻止疾病发展和进展的治疗方法。无论疾病的根本原因是什么,年龄是患上这些疾病的最强危险因素,这表明衰老大脑中发生的变化使其更容易患上神经退行性疾病。此外,由于衰老大脑中发生了许多不同的变化,因此靶向单一变化不太可能对疾病治疗有效。因此,需要具有多种生物学活性的化合物,这些化合物可以影响导致神经退行性疾病发展和进展的与年龄相关的大脑变化。植物来源的类黄酮具有广泛的活性,这使它们在阻止与神经退行性疾病相关的与年龄相关的毒性途径方面特别有效。在这篇综述中,介绍了多种类黄酮在 AD、PD、HD 和 ALS 模型中的有益作用的证据,并确定了共同的作用机制。总的来说,临床前数据强烈支持进一步研究特定类黄酮治疗神经退行性疾病。