Apolipoprotein-mimetic nanodiscs reduce lipid accumulation and improve liver function in acid sphingomyelinase deficiency.
Apolipoprotein-mimetic nanodiscs reduce lipid accumulation and improve liver function in acid sphingomyelinase deficiency.
复制标题
DOI：
10.1016/j.nano.2023.102705
复制
发表时间：
2023-09
影响因子：
5.4
通讯作者：
Schwendeman, Anna
中科院分区：
文献类型：
--
作者：
Halseth, Troy A.;Correia, Adele B.;Schultz, Mark L.;V. Fawaz, Maria;Kuiper, Esmee Q.;Kumaran, Preethi;Dorsey, Kristen Hong;Schuchman, Edward H.;Lieberman, Andrew P.;Schwendeman, Anna
酸性鞘磷脂酶缺乏症（ASMD）是由酸性鞘磷脂酶活性降低引起的严重脂质储存障碍。ASMD的特征在于鞘磷脂在晚期内体和溶酶体中的积累，导致进行性神经功能障碍和肝脾肿大。我们的目的是研究合成的载脂蛋白A-I（ApoA-I）模拟物作为脂质清除剂治疗ASMD的效用。我们确定了先导肽22 A可以以剂量依赖性方式减少ASMD患者皮肤成纤维细胞中的鞘磷脂积累。在ASMD小鼠模型中，腹膜内施用配制为合成高密度脂蛋白（sHDL）纳米盘的22 A将鞘磷脂从外周组织动员到循环中并改善肝功能。总之，我们的数据表明，载脂蛋白模拟物可以作为一种新的治疗策略，用于调节ASMD中观察到的病理学。合成高密度脂蛋白纳米盘在ASMD小鼠模型中接受来自外周组织的过量鞘磷脂。
Acid sphingomyelinase deficiency (ASMD) is a severe lipid storage disorder caused by the diminished activity of the acid sphingomyelinase enzyme. ASMD is characterized by the accumulation of sphingomyelin in late endosomes and lysosomes leading to progressive neurological dysfunction and hepatosplenomegaly. Our objective was to investigate the utility of synthetic apolipoprotein A-I (ApoA-I) mimetics designed to act as lipid scavengers for the treatment of ASMD. We determined the lead peptide, 22A, could reduce sphingomyelin accumulation in ASMD patient skin fibroblasts in a dose dependent manner. Intraperitoneal administration of 22A formulated as a synthetic high-density lipoprotein (sHDL) nanodisc mobilized sphingomyelin from peripheral tissues into circulation and improved liver function in a mouse model of ASMD. Together, our data demonstrates that apolipoprotein mimetics could serve as a novel therapeutic strategy for modulating the pathology observed in ASMD. Synthetic high-density lipoprotein nanodiscs accept excess sphingomyelin from peripheral tissues in a mouse model of ASMD.
登录
查看更多内容
DOI：
10.1016/j.beem.2014.10.002
发表时间：
2015-03-01
影响因子：
7.4
作者：
Schuchman, Edward H.;Wasserstein, Melissa P.
通讯作者：
Wasserstein, Melissa P.
DOI：
10.1124/jpet.110.167890
发表时间：
2010-08-10
影响因子：
3.5
作者：
Amar, Marcelo J. A.;D'Souza, Wilissa;Remaley, Alan T.
通讯作者：
Remaley, Alan T.
影响因子：
24
作者：
Nicholls, Stephen J.;Andrews, Jordan;Butters, Julie
通讯作者：
Butters, Julie
影响因子：
6.5
作者：
Lee, CY;Lesimple, A;Marcil, M
通讯作者：
Marcil, M
影响因子：
5.1
作者：
McGovern, MM;Pohl-Worgall, T;Wasserstein, MP
通讯作者：
Wasserstein, MP