生物谷報(bào)道：有兩個(gè)息息相關(guān)的消息令人有點(diǎn)矛盾,，好消息是我們的平均壽命越來(lái)越長(zhǎng),；壞消息是我們活的越長(zhǎng),，患晚發(fā)性阿爾茨海默癥的幾率就越高,。
許多阿爾茨海默癥研究人那么一直都在鼓吹魚(yú)油的好處,，認(rèn)為魚(yú)油能夠延緩或預(yù)防這種疾病的發(fā)生?，F(xiàn)在,，來(lái)自美國(guó)加州大學(xué)洛杉磯分校的研究人員證實(shí)魚(yú)油確實(shí)能夠?qū)拱柎暮ＤY，并且找到了這種功效的背后原因,。
在最新一期的Journal of Neuroscience雜志上,，來(lái)自美國(guó)加州大學(xué)洛杉磯分校David Geffen醫(yī)學(xué)院的醫(yī)學(xué)和神經(jīng)學(xué)教授Greg Cole和同事報(bào)道說(shuō)，魚(yú)油中的omega-3脂肪酸二十二碳六烯酸（DHA）能夠增加LR11的產(chǎn)量,。LR11蛋白在阿爾茨海默癥患者中明顯減少,，并且這種蛋白能夠破壞形成與該病有關(guān)的斑塊的蛋白質(zhì)。
阿爾茨海默癥是一種能導(dǎo)致記憶力減退,、癡呆,、個(gè)性轉(zhuǎn)變和死亡的神經(jīng)退化疾病。據(jù)美國(guó)阿爾茨海默癥協(xié)會(huì)估計(jì),，目前大約有510萬(wàn)美國(guó)人受這種疾病的折磨,，該協(xié)會(huì)還預(yù)測(cè)這個(gè)數(shù)據(jù)到2050年會(huì)增加到1100萬(wàn)至1600萬(wàn)。
研究人員在多個(gè)生物系統(tǒng)中分析了魚(yú)油或DHA的效果,，他們將魚(yú)油或DHA添加到食物中或直接添加到實(shí)驗(yàn)室培養(yǎng)的神經(jīng)元中,。他們發(fā)現(xiàn)，即使低劑量的DNA也能增加大鼠神經(jīng)元中的LR11水平,，而食物中的DNA則能增加大鼠或年老小鼠大腦中的LR11量,。這些試驗(yàn)鼠已經(jīng)通過(guò)基因工程手段使其患上了阿爾茨海默癥。
為了驗(yàn)證DHA的益處不僅限于非人類(lèi)動(dòng)物細(xì)胞,，研究人員還證實(shí)了DHA對(duì)實(shí)驗(yàn)室中培養(yǎng)的人類(lèi)神經(jīng)元的直接影響,。研究人員指出，高水平的DHA導(dǎo)致產(chǎn)生的LR11似乎能夠預(yù)防阿爾茨海默癥,。而低水平的LR11能導(dǎo)致淀粉體斑塊的形成,。
脂肪酸（如DHA）被認(rèn)為是關(guān)鍵的脂肪酸，其原因是身體不能利用其他資源制造這些脂肪酸,，因此必須通過(guò)攝入食物來(lái)獲取,。多年的研究顯示，DHA是在大腦中的含量最為豐富,，并且是胎兒和嬰兒大腦發(fā)育的關(guān)鍵物質(zhì),。此前大量的研究將大腦中低水平的DHA與認(rèn)知損傷聯(lián)系在一起，并且證實(shí)DHA水平較低可能增加阿爾茨海默癥患者大腦中的氧化壓力,。
在這些結(jié)果的基礎(chǔ)上,，美國(guó)衛(wèi)生研究院目前正在進(jìn)行一項(xiàng)大規(guī)模的臨床試驗(yàn)來(lái)檢測(cè)DHA對(duì)阿爾茨海默癥的影響。研究人員表示,，雖然對(duì)這些患者來(lái)說(shuō),，DHA的效果可能很有限，但是他希望NIH能夠進(jìn)行大規(guī)模的魚(yú)油預(yù)防臨床試驗(yàn),。
原始出處：
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: [email protected]
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: [email protected]
