Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity.
Preventive effects of a fermented dairy product against Alzheimer's disease and identification of a novel oleamide with enhanced microglial phagocytosis and anti-inflammatory activity.
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发酵乳制品对阿尔茨海默氏病的预防作用，并鉴定出具有增强的小胶质细胞增多症和抗炎活性的新型Oleamide。
DOI：
10.1371/journal.pone.0118512
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发表时间：
2015
期刊：
影响因子：
3.7
通讯作者：
Nakayama H
中科院分区：
文献类型：
--
作者：
Ano Y;Ozawa M;Kutsukake T;Sugiyama S;Uchida K;Yoshida A;Nakayama H
尽管全世界痴呆症患者数量不断增加，但针对这种疾病的基本治疗方法尚未建立。流行病学研究表明，摄入发酵乳制品可以预防老年人的认知能力下降。然而，造成这种效果的活性化合物仍有待阐明。本研究旨在阐明乳制品对阿尔茨海默氏病的预防作用并确定其致病成分。在此，在阿尔茨海默氏病 (5xFAD) 小鼠模型中，摄入白青霉发酵的乳制品通过减少 β 淀粉样蛋白 (Aβ) 的积累和海马炎症（TNF-α 和 MIP-1α 的产生）以及增强海马神经营养因子（BDNF 和 GDNF）来预防该疾病。对发酵乳制品中预防物质的研究发现，油酰胺是一种新型双活性成分，可增强小胶质细胞 Aβ 的吞噬作用以及体内外对 LPS 刺激的抗炎活性。在发酵过程中，通过脂肪酶的酶促酰胺化，由油酸合成油酰胺，油酸是一般乳制品的丰富成分。本研究证明了乳制品对阿尔茨海默病的预防作用，而此前这种疾病仅在流行病学上有报道。此外，油酰胺已被确定为乳制品的活性成分，被认为可以通过增强小胶质细胞的吞噬作用来减少 Aβ 积累，并抑制 Aβ 沉积后的小胶质细胞炎症。由于卡门培尔奶酪等发酵乳制品很容易作为日常膳食安全摄入，因此食用它们可能是预防痴呆症的一种策略。
Despite the ever-increasing number of patients with dementia worldwide, fundamental therapeutic approaches to this condition have not been established. Epidemiological studies suggest that intake of fermented dairy products prevents cognitive decline in the elderly. However, the active compounds responsible for the effect remain to be elucidated. The present study aims to elucidate the preventive effects of dairy products on Alzheimer’s disease and to identify the responsible component. Here, in a mouse model of Alzheimer’s disease (5xFAD), intake of a dairy product fermented with Penicillium candidum had preventive effects on the disease by reducing the accumulation of amyloid β (Aβ) and hippocampal inflammation (TNF-α and MIP-1α production), and enhancing hippocampal neurotrophic factors (BDNF and GDNF). A search for preventive substances in the fermented dairy product identified oleamide as a novel dual-active component that enhanced microglial Aβ phagocytosis and anti-inflammatory activity towards LPS stimulation in vitro and in vivo. During the fermentation, oleamide was synthesized from oleic acid, which is an abundant component of general dairy products owing to lipase enzymatic amidation. The present study has demonstrated the preventive effect of dairy products on Alzheimer’s disease, which was previously reported only epidemiologically. Moreover, oleamide has been identified as an active component of dairy products that is considered to reduce Aβ accumulation via enhanced microglial phagocytosis, and to suppress microglial inflammation after Aβ deposition. Because fermented dairy products such as camembert cheese are easy to ingest safely as a daily meal, their consumption might represent a preventive strategy for dementia.
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DOI：
10.1523/jneurosci.5268-11.2012
发表时间：
2012-07-25
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Mandrekar-Colucci S;Karlo JC;Landreth GE
通讯作者：
Landreth GE
影响因子：
6.2
作者：
Blank, Thomas;Prinz, Marco
通讯作者：
Prinz, Marco
影响因子：
3.3
作者：
Lee, C. Y. Daniel;Landreth, Gary E.
通讯作者：
Landreth, Gary E.
影响因子：
6.2
作者：
Malm, Tarja;Koistinaho, Milla;Koistinaho, Jari
通讯作者：
Koistinaho, Jari
影响因子：
7.3
作者：
Lu, P.;Mamiya, T.;Nabeshima, T.
通讯作者：
Nabeshima, T.