近些年,，低密度脂蛋白受體（LDLR）獲得了很高的關(guān)注,，主要是因?yàn)樗c冠狀動(dòng)脈心臟疾病和動(dòng)脈粥樣硬化有關(guān)。根據(jù)發(fā)布在12月10日Neuron上的一篇文章,，LDLR似乎也與退化性大腦疾病有關(guān),。這項(xiàng)新的研究表明，LDLR能減少與老年癡呆（AD）相關(guān)的大腦變化,，該研究為這類(lèi)無(wú)法治愈的疾病提供了新的治療策略,。
淀粉樣β蛋白（Aβ）是引起AD的主要原因，Aβ堆積會(huì)造成神經(jīng)元的破壞,，因此它被認(rèn)為是疾病發(fā)病機(jī)理的首要因素,。此外，載脂蛋白E(apoE),，是一個(gè)已經(jīng)確定的晚發(fā)型AD的遺傳風(fēng)險(xiǎn)因子,，其參與脂肪的代謝和運(yùn)輸。先前的研究已經(jīng)涉及Aβ堆積中的apoE,。
調(diào)節(jié)控制apoE代謝的蛋白功能將可能改變淀粉樣堆積的范圍,，并最終影響疾病的發(fā)展。這項(xiàng)研究的負(fù)責(zé)人是來(lái)自華盛頓大學(xué)醫(yī)學(xué)院的David M. Holtzman博士,，據(jù)他介紹,，低密度的脂蛋白受體能夠綁定到apoE上，但是其對(duì)AD發(fā)病機(jī)制的潛在影響還不是很清楚,。
Holtzman博士和他的同事基因改造了一種大腦中LDLR過(guò)表達(dá)的老鼠,，使其表現(xiàn)出與AD相關(guān)的病理學(xué)變化。結(jié)果發(fā)現(xiàn),，LDLR過(guò)表達(dá)導(dǎo)致了Aβ聚集的減少,，淀粉狀蛋白斑的形成，并出現(xiàn)神經(jīng)炎癥反應(yīng),。
該研究結(jié)果清晰地表明了大腦中LDLR過(guò)表達(dá)的有利影響,，或有助于在未來(lái)開(kāi)發(fā)出新的退化型神經(jīng)疾病治療藥物，對(duì)外周組織中的LDLR進(jìn)行調(diào)控,。（生物谷Bioon.com）
生物谷推薦原始出處：
Neuron, Volume 63, doi:10.1016/j.neuron.2009.06.026
The Role of Apolipoprotein E in Alzheimer's Disease
Jungsu Kim1, Jacob M. Basak1 and David M. Holtzman1, ,
1 Department of Neurology, Developmental Biology, Hope Center for Neurological Disorders, Alzheimer's Disease Research Center, Washington University School of Medicine, St. Louis, MO 63110, USA
The ε4 allele of apolipoprotein E (APOE) is the major genetic risk factor for Alzheimer's disease (AD). Although there have been numerous studies attempting to elucidate the underlying mechanism for this increased risk, how apoE4 influences AD onset and progression has yet to be proven. However, prevailing evidence suggests that the differential effects of apoE isoforms on Aβ aggregation and clearance play the major role in AD pathogenesis. Other potential mechanisms, such as the differential modulation of neurotoxicity and tau phosphorylation by apoE isoforms as well as its role in synaptic plasticity and neuroinflammation, have not been ruled out. Inconsistent results among studies have made it difficult to define whether the APOE ε4 allele represents a gain of toxic function, a loss of neuroprotective function, or both. Therapeutic strategies based on apoE propose to reduce the toxic effects of apoE4 or to restore the physiological, protective functions of apoE.
