Therapeutic strategy for Niemann-Pick disease type C focusing on induction of ACAT1-positive late endosomes

2014 Fiscal Year Final Research Report

• Project/Area Number: 23590448
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: The University of Tokushima
• Principal Investigator: SAKASHITA Naomi 徳島大学, ヘルスバイオサイエンス研究部, 教授 (90284752)
• Co-Investigator(Kenkyū-buntansha): TAKEYA Motohiro 熊本大学, 大学院生命科学研究部, 教授 (90155052)
• Project Period (FY): 2011-04-28 – 2015-03-31
• Keywords: C型Niemann-Pick病 / マクロファージ / ACAT1 / 後期エンドゾーム / コレステロール / NPC1

Outline of Final Research Achievements

Niemann-Pick disease type C (NPC1-/-) is lysosomal storage disease resulting from deficiency of intracellular cholesterol trafficking protein NPC1, which accumulates massive cholesterol in late endosome and cause cellular/tissue injury. We tried to rescue NPC1-/- employing induction of ACAT1-positive late endosomes (ACAT1-LE) to the NPC1-/- mice. Induction of ACAT1-LE to NPC1-/- macrophages resulted in decrease of free cholesterol and increase of cholesteryl ester. Induction of ACAT1-LE to NPC1-/- neonates by administration of methyl-beta-cycrodextrin-cholesterol complex improved life span of the mice. These results suggested that efficient ACAT1-LE induction is essential for NPC-/- therapeutic strategy.

Free Research Field

病理学