Department of Nanobiomedical Science, College of Advanced Science, Dankook University, Chungnam, Korea.
Arch Pharm Res. 2010 Oct;33(10):1589-609. doi: 10.1007/s12272-010-1010-y. Epub 2010 Oct 30.
The average human life span in developed countries has increased to more than 80 years following rapid breakthrough and developments in modern medicine and science, resulting in prolonged life expectancy and increase in the population counts of the geriatric age group. This translates into a dramatic increase in disease burden of elderly patients suffering from senile disorders including neurodegenerative diseases, particularly Alzheimer's disease (AD). AD is characterized by the death of nerve cells in the cerebral cortex and is the most common subtype of dementia that affected 25 million people worldwide in 2000 and is expected to increase to 114 million by 2050. Despite the exponential growth in the number of AD patients, only acetylcholinesterase (AChE) inhibitors are being currently used to treat AD. It is well known that AChE inhibitors can alleviate the symptoms of AD but not halt the disease progression. Consequently, therapeutic agents against AD acting at various pathologic levels are needed. In the recent decade, natural products with anti-AD properties have attracted much attention. But very few natural products have been investigated in a scientifically justifiable method for these biological activities. Following a detailed research process, it is certain that natural products have a strong potential to develop biologically active compounds with new chemical structures. Many studies have been carried out to identify the naturally occurring anti-AD agents. This review article describes the molecular targets aiming at developing the anti-AD agents including the inhibition of AChE, inhibition of Aβ production by enhancing α-secretase (non-amyloidogenic pathway) or inhibiting β- and γ-secretases (amyloidogenic pathway), alleviating Aβ-induced neurotoxicity or reducing Aβ-induced neuroinflammation. In addition, this paper summarizes the potential of some of the natural products that might inhibit specific molecular targets and slow the progression of this disease.
在现代医学和科学的快速突破和发展下,发达国家的人类平均寿命已延长至 80 多岁以上,这导致了预期寿命的延长和老年人口的增加。这意味着患有老年疾病(包括神经退行性疾病,尤其是阿尔茨海默病)的老年患者的疾病负担显著增加。AD 的特征是大脑皮层神经细胞死亡,是 2000 年全球受影响的 2500 万人中最常见的痴呆症类型,预计到 2050 年将增加到 1.14 亿。尽管 AD 患者的数量呈指数级增长,但目前仅使用乙酰胆碱酯酶(AChE)抑制剂来治疗 AD。众所周知,AChE 抑制剂可以缓解 AD 的症状,但不能阻止疾病的进展。因此,需要针对 AD 的各种病理水平的治疗药物。在最近十年中,具有抗 AD 特性的天然产物引起了广泛关注。但是,很少有天然产物以科学合理的方法针对这些生物活性进行了研究。经过详细的研究过程,可以肯定的是,天然产物具有很强的潜力来开发具有新化学结构的生物活性化合物。已经进行了许多研究来鉴定天然存在的抗 AD 试剂。本文综述了旨在开发抗 AD 药物的分子靶标,包括抑制 AChE、通过增强α-分泌酶(非淀粉样蛋白形成途径)抑制 Aβ产生或抑制β-和γ-分泌酶(淀粉样蛋白形成途径)、缓解 Aβ诱导的神经毒性或减少 Aβ诱导的神经炎症。此外,本文总结了一些天然产物的潜力,这些天然产物可能抑制特定的分子靶标并减缓该疾病的进展。