Yu Man-Shan, Lai Cora Sau-Wan, Ho Yuen-Shan, Zee Sze-Yong, So Kwok-Fai, Yuen Wai-Hung, Chang Raymond Chuen-Chung
Laboratory of Neurodegenerative Diseases, Department of Anatomy, LKS Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, P.R. China.
Int J Mol Med. 2007 Aug;20(2):261-8.
Alzheimer's disease (AD) is an age-related neurodegenerative disease. There are increasing lines of evidence showing that the molecular signaling pathways in aged cells are altered so that cells are susceptible to injury. We and other laboratories have demonstrated the significant involvement of double-stranded RNA-dependent protein kinase (PKR) in beta-amyloid (A beta) peptide neurotoxicity and in AD. Fructus lycii (the fruit of Lycium barbarum) has long been used in oriental medicine as an anti-aging agent. Our previous studies demonstrated that the aqueous extract isolated from L. barbarum exhibited significant protection on cultured neurons against harmful chemical toxins such as A beta and dithiothreitol. We also showed that the polysaccharide-containing extract (LBP) from L. barbarum exhibited neuroprotective effects in the retina against ocular hypertension in a laser-induced glaucoma animal model. In this study, we aimed to investigate whether LBP can elicit neuroprotection to neurons stressed by A beta peptides. Furthermore, we planned to isolate and identify the neuroprotective agent from LBP using chromatographic methods. Our results showed that pretreatment of LBP effectively protected neurons against A beta-induced apoptosis by reducing the activity of both caspase-3 and -2, but not caspase-8 and -9. A new arabinogalactan-protein (LBP-III) was isolated from LBP and attenuated A beta peptide-activated caspase-3-like activity. LBP-III markedly reduced the phosphorylation of PKR triggered by A beta peptide. Since the phosphorylation state of PKR increased with age, reduction of its phosphorylation triggered by A beta peptide may implicate that LBP-III from Fructus lycii is a potential neuroprotective agent in AD. As herbal medicine has received increasing attention for the treatment of AD, our study will open a window for the development of a neuroprotective agent for anti-aging from Chinese medicine.
阿尔茨海默病（AD）是一种与年龄相关的神经退行性疾病。越来越多的证据表明，衰老细胞中的分子信号通路发生改变，使得细胞易于受到损伤。我们实验室和其他实验室已证明双链RNA依赖性蛋白激酶（PKR）在β-淀粉样蛋白（Aβ）肽神经毒性及AD中起重要作用。枸杞（枸杞的果实）长期以来在东方医学中被用作抗衰老剂。我们之前的研究表明，从枸杞中分离出的水提取物对培养的神经元具有显著的保护作用，可抵御有害化学毒素，如Aβ和二硫苏糖醇。我们还表明，枸杞中含多糖的提取物（LBP）在激光诱导的青光眼动物模型中，对视网膜具有抗高眼压的神经保护作用。在本研究中，我们旨在调查LBP是否能对受Aβ肽胁迫的神经元产生神经保护作用。此外，我们计划使用色谱方法从LBP中分离并鉴定神经保护剂。我们的结果表明，LBP预处理通过降低半胱天冬酶-3和-2的活性，但不降低半胱天冬酶-8和-9的活性，有效保护神经元免受Aβ诱导的凋亡。从LBP中分离出一种新的阿拉伯半乳聚糖蛋白（LBP-III），它可减弱Aβ肽激活的半胱天冬酶-3样活性。LBP-III显著降低了Aβ肽触发的PKR磷酸化。由于PKR的磷酸化状态随年龄增加，Aβ肽触发的其磷酸化的降低可能意味着枸杞中的LBP-III是AD中一种潜在的神经保护剂。随着草药在AD治疗中受到越来越多的关注，我们的研究将为开发一种来自中药的抗衰老神经保护剂打开一扇窗。
