生物谷报道:有两个息息相关的消息令人有点矛盾,好消息是我们的平均寿命越来越长;坏消息是我们活的越长,患晚发性阿尔茨海默症的几率就越高。
许多阿尔茨海默症研究人那么一直都在鼓吹鱼油的好处,认为鱼油能够延缓或预防这种疾病的发生。现在,来自美国加州大学洛杉矶分校的研究人员证实鱼油确实能够对抗阿尔茨海默症,并且找到了这种功效的背后原因。
在最新一期的Journal of Neuroscience杂志上,来自美国加州大学洛杉矶分校David Geffen医学院的医学和神经学教授Greg Cole和同事报道说,鱼油中的omega-3脂肪酸二十二碳六烯酸(DHA)能够增加LR11的产量。LR11蛋白在阿尔茨海默症患者中明显减少,并且这种蛋白能够破坏形成与该病有关的斑块的蛋白质。
阿尔茨海默症是一种能导致记忆力减退、痴呆、个性转变和死亡的神经退化疾病。据美国阿尔茨海默症协会估计,目前大约有510万美国人受这种疾病的折磨,该协会还预测这个数据到2050年会增加到1100万至1600万。
研究人员在多个生物系统中分析了鱼油或DHA的效果,他们将鱼油或DHA添加到食物中或直接添加到实验室培养的神经元中。他们发现,即使低剂量的DNA也能增加大鼠神经元中的LR11水平,而食物中的DNA则能增加大鼠或年老小鼠大脑中的LR11量。这些试验鼠已经通过基因工程手段使其患上了阿尔茨海默症。
为了验证DHA的益处不仅限于非人类动物细胞,研究人员还证实了DHA对实验室中培养的人类神经元的直接影响。研究人员指出,高水平的DHA导致产生的LR11似乎能够预防阿尔茨海默症。而低水平的LR11能导致淀粉体斑块的形成。
脂肪酸(如DHA)被认为是关键的脂肪酸,其原因是身体不能利用其他资源制造这些脂肪酸,因此必须通过摄入食物来获取。多年的研究显示,DHA是在大脑中的含量最为丰富,并且是胎儿和婴儿大脑发育的关键物质。此前大量的研究将大脑中低水平的DHA与认知损伤联系在一起,并且证实DHA水平较低可能增加阿尔茨海默症患者大脑中的氧化压力。
在这些结果的基础上,美国卫生研究院目前正在进行一项大规模的临床试验来检测DHA对阿尔茨海默症的影响。研究人员表示,虽然对这些患者来说,DHA的效果可能很有限,但是他希望NIH能够进行大规模的鱼油预防临床试验。
原始出处:
The Journal of Neuroscience, December 26, 2007, 27(52):14299-14307; doi:10.1523/JNEUROSCI.3593-07.2007
Omega-3 Fatty Acid Docosahexaenoic Acid Increases SorLA/LR11, a Sorting Protein with Reduced Expression in Sporadic Alzheimer's Disease (AD): Relevance to AD Prevention
Qiu-Lan Ma,1,3 Bruce Teter,1,3 Oliver J. Ubeda,1,3 Takashi Morihara,1,3,4 Dilsher Dhoot,1,3 Michael D. Nyby,1 Michael L. Tuck,1 Sally A. Frautschy,1,2,3 and Greg M. Cole1,2,3
Departments of 1Medicine and 2Neurology, University of California, Los Angeles, California 90095, 3Geriatric Research, Education and Clinical Center, Veterans Affairs, Greater Los Angeles Healthcare System, North Hills, California 91343, and 4Department of Post-Genomics and Diseases, Division of Psychiatry and Behavioral Proteomics, Osaka University Graduate School of Medicine D3, Suita-shi, Osaka 565-0871, Japan
Correspondence should be addressed to Greg M. Cole, Veterans Affairs, Greater Los Angeles Healthcare System Research 151, Building 7, Room A101, 16111 Plummer Street, North Hills, CA 91343. Email: gmcole@ucla.edu
Environmental and genetic factors, notably ApoE4, contribute to the etiology of late-onset Alzheimer's disease (LOAD). Reduced mRNA and protein for an apolipoprotein E (ApoE) receptor family member, SorLA (LR11) has been found in LOAD but not early-onset AD, suggesting that LR11 loss is not secondary to pathology. LR11 is a neuronal sorting protein that reduces amyloid precursor protein (APP) trafficking to secretases that generate β-amyloid (Aβ). Genetic polymorphisms that reduce LR11 expression are associated with increased AD risk. However these polymorphisms account for only a fraction of cases with LR11 deficits, suggesting involvement of environmental factors. Because lipoprotein receptors are typically lipid-regulated, we postulated that LR11 is regulated by docosahexaenoic acid (DHA), an essential -3 fatty acid related to reduced AD risk and reduced Aβ accumulation. In this study, we report that DHA significantly increases LR11 in multiple systems, including primary rat neurons, aged non-Tg mice and an aged DHA-depleted APPsw AD mouse model. DHA also increased LR11 in a human neuronal line. In vivo elevation of LR11 was also observed with dietary fish oil in young rats with insulin resistance, a model for type II diabetes, another AD risk factor. These data argue that DHA induction of LR11 does not require DHA-depleting diets and is not age dependent. Because reduced LR11 is known to increase Aβ production and may be a significant genetic cause of LOAD, our results indicate that DHA increases in SorLA/LR11 levels may play an important role in preventing LOAD.
Key words: SorLA; LR11; Alzheimer; docosahexaenoic acid; diet; omega-3 fatty acid; amyloid
Correspondence should be addressed to Greg M. Cole, Veterans Affairs, Greater Los Angeles Healthcare System Research 151, Building 7, Room A101, 16111 Plummer Street, North Hills, CA 91343. Email: gmcole@ucla.edu