Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer's disease mouse model.
Stearoyl-CoA Desaturase inhibition reverses immune, synaptic and cognitive impairments in an Alzheimer's disease mouse model.
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硬脂酰辅酶a去饱和酶抑制逆转阿尔茨海默病小鼠模型的免疫、突触和认知障碍。
DOI：
10.1038/s41467-022-29506-y
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发表时间：
2022-04-20
影响因子：
16.6
通讯作者：
中科院分区：
文献类型：
--
作者：
阿尔茨海默病 (AD) 的定义特征包括蛋白质聚集、免疫、脂质代谢、突触以及学习和记忆的改变。其中，脂质异常是人们了解最少的。在这里，我们研究了硬脂酰辅酶 A 去饱和酶 (SCD)（脂肪酸去饱和的关键调节因子）在 AD 发病机制中的作用。我们发现，在 AD 3xTg 小鼠模型中抑制大脑 SCD 活动 1 个月会改变海马中与 AD 相关的核心转录组通路，同时恢复海马功能的重要组成部分，包括树突棘和结构、即早期基因表达以及学习和记忆本身。此外，SCD 抑制会抑制小胶质细胞的激活，小胶质细胞是 AD 期间脊柱损失的关键介质，也是大脑的主要免疫细胞。这些数据表明，脑脂肪酸代谢将 AD 基因与下游免疫、突触和功能损伤联系起来，将 SCD 确定为 AD 治疗的潜在目标。阿尔茨海默氏病 (AD) 的特点是脂质异常，但目前尚不清楚。在此，作者研究了硬脂酰辅酶 A 去饱和酶 (SCD) 在 AD 小鼠模型中的作用。他们表明，抑制 SCD 活性会引起大脑和免疫细胞的主要转录变化，并恢复树突结构以及学习和记忆。
The defining features of Alzheimer’s disease (AD) include alterations in protein aggregation, immunity, lipid metabolism, synapses, and learning and memory. Of these, lipid abnormalities are the least understood. Here, we investigate the role of Stearoyl-CoA desaturase (SCD), a crucial regulator of fatty acid desaturation, in AD pathogenesis. We show that inhibiting brain SCD activity for 1-month in the 3xTg mouse model of AD alters core AD-related transcriptomic pathways in the hippocampus, and that it concomitantly restores essential components of hippocampal function, including dendritic spines and structure, immediate-early gene expression, and learning and memory itself. Moreover, SCD inhibition dampens activation of microglia, key mediators of spine loss during AD and the main immune cells of the brain. These data reveal that brain fatty acid metabolism links AD genes to downstream immune, synaptic, and functional impairments, identifying SCD as a potential target for AD treatment. Alzheimer’s disease (AD) is characterized by lipid abnormalities which are not well understood. Here, the authors investigate the role of Stearoyl-CoA desaturase (SCD) in a mouse model of AD. They show that inhibiting SCD activity induces major brain and immune cell transcriptional changes and restores dendritic structure and learning and memory.
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DOI：
10.1093/bioinformatics/btu638
发表时间：
2015-01-15
期刊：
Bioinformatics (Oxford, England)
影响因子：
--
作者：
Anders S;Pyl PT;Huber W
通讯作者：
Huber W
影响因子：
25
作者：
Chang, Michael C.;Park, Joo Min;Pelkey, Kenneth A.;Grabenstatter, Heidi L.;Xu, Desheng;Linden, David J.;Sutula, Thomas P.;McBain, Chris J.;Worley, Paul F.
通讯作者：
Worley, Paul F.
影响因子：
14
作者：
de Wilde, Martijn C.;Overk, Cassia R.;Sijben, John W.;Masliah, Eliezer
通讯作者：
Masliah, Eliezer
影响因子：
16.2
作者：
Chowdhury, Shoaib;Shepherd, Jason D.;Worley, Paul F.
通讯作者：
Worley, Paul F.
影响因子：
4.2
作者：
Caruso, Donatella;Barron, Anna M.;Melcangi, Roberto C.
通讯作者：
Melcangi, Roberto C.