Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease.
Exosome reduction in vivo is associated with lower amyloid plaque load in the 5XFAD mouse model of Alzheimer's disease.
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DOI：
10.1016/j.neurobiolaging.2014.02.012
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发表时间：
2014-08
影响因子：
4.2
通讯作者：
Bieberich E
中科院分区：
文献类型：
--
作者：
Dinkins MB;Dasgupta S;Wang G;Zhu G;Bieberich E
我们在此提供的证据表明，外泌体在体外和体内刺激Aβ1-42的聚集，并在体外干扰原代培养的星形胶质细胞和小胶质细胞对Aβ的摄取。通过使用GW 4869抑制中性鞘磷脂酶2（nSMase 2）（一种从鞘磷脂生成神经酰胺的关键调节酶）来阻止外泌体分泌。使用5XFAD小鼠，我们表明腹膜内注射GW 4869降低了脑和血清外泌体、脑神经酰胺和Aβ1-42斑块负荷的水平。雄性小鼠中总Aβ1-42以及脑切片中斑块数量的减少显著大于雌性小鼠（减少40%）。我们的研究结果表明，GW 4869通过阻止外泌体分泌减少体内淀粉样斑块的形成，并通过干扰外泌体分泌将nSM酶2鉴定为AD中的潜在药物靶点。
We present evidence here that exosomes stimulate aggregation of Aβ1-42 in vitro and in vivo and interfere with uptake of Aβ by primary cultured astrocytes and microglia in vitro. Exosome secretion is prevented by inhibition of neutral sphingomyelinase 2 (nSMase2), a key regulatory enzyme generating ceramide from sphingomyelin, with GW4869. Using the 5XFAD mouse, we show that intraperitoneal injection of GW4869 reduces the levels of brain and serum exosomes, brain ceramide, and Aβ1-42 plaque load. Reduction of total Aβ1-42 as well as number of plaques in brain sections was significantly greater (40% reduction) in male than female mice. Our results suggest that GW4869 reduces amyloid plaque formation in vivo by preventing exosome secretion and identifies nSMase2 as potential drug target in AD by interfering with exosome secretion.
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DOI：
10.1523/jneurosci.1243-10.2010
发表时间：
2010-09-22
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Jana A;Pahan K
通讯作者：
Pahan K
影响因子：
82.9
作者：
HAASS, C;LEMERE, CA;SELKOE, DJ
通讯作者：
SELKOE, DJ
DOI：
10.1073/pnas.1209414109
发表时间：
2012-07-31
影响因子：
11.1
作者：
Fabbri, Muller;Paone, Alessio;Croce, Carlo M.
通讯作者：
Croce, Carlo M.
影响因子：
6.5
作者：
Krishnamurthy, Karman;Dasgupta, Somsankar;Bieberich, Erhard
通讯作者：
Bieberich, Erhard
影响因子：
3.7
作者：
Khan S;Jutzy JM;Valenzuela MM;Turay D;Aspe JR;Ashok A;Mirshahidi S;Mercola D;Lilly MB;Wall NR
通讯作者：
Wall NR