尼曼-皮克病,C型
NPC1
尼曼-皮克病
胆固醇
鞘磷脂
内分泌学
内科学
卵磷脂
化学
环糊精
肝脾肿大
神经节苷脂
内体
脾脏
医学
生物化学
疾病
细胞内
作者
Takumi Nishida,Ryoma Yokoyama,Yuto Kubohira,Yuki Maeda,Toru Takeo,Naomi Nakagata,Hiroki Takagi,Kandai Ishikura,K. Yanagihara,Shogo Misumi,Naoki Kishimoto,Yoichi Ishitsuka,Yuki Kondo,Tetsumi Irie,Minami Soga,Takumi Era,Risako Onodera,Taishi Higashi,Keiichi Motoyama
出处
期刊:ACS applied bio materials
[American Chemical Society]
日期:2022-05-04
卷期号:5 (5): 2377-2388
被引量:6
标识
DOI:10.1021/acsabm.2c00233
摘要
Niemann-Pick disease type C (NPC) is characterized by the accumulation of glycolipids such as free cholesterol, sphingomyelin, and gangliosides in late endosomes/lysosomes (endolysosomes) due to abnormalities in the membrane proteins NPC1 or NPC2. The main symptoms of NPC caused by free cholesterol accumulation in various tissues vary depending on the time of onset, but hepatosplenomegaly and neurological symptoms accompanied by decreased motor, cognitive, and mental functions are observed in all age groups. However, the efficacy of NPC treatment remains limited. Herein, we have fabricated lactose-appended hydroxypropyl-β-cyclodextrin (Lac-HPβCD) and evaluated its lowering effects on cholesterol accumulation in NPC model mice. We reveal that Lac-HPβCD lowers cholesterol accumulation in the liver and spleen by reducing the amount of free cholesterol. Moreover, Lac-HPβCD reduces the amount of free cholesterol in the cerebrum and slightly alleviates motor dysfunction. These results suggest that Lac-HPβCD has potential for the treatment of NPC.
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