Study on mechanisms of inflammation in the central nervous system of gangliosidosis

2013 Fiscal Year Final Research Report

• Project/Area Number: 23590468
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Experimental pathology
• Research Institution: Yokohama City University
• Principal Investigator: YAMANAKA Shoji 横浜市立大学, 附属病院, 准教授 (80264604)
• Co-Investigator(Kenkyū-buntansha): YAMAGUCHI Akira 横浜市立大学, 医学研究科, 客員研究員 (20381585)
• Project Period (FY): 2011 – 2013
• Keywords: GM2ガングリオシドーシス / サンドホフ病 / Toll like receptor / 炎症

Research Abstract

Sandhoff disease is a lysosomal storage disorder characterized by the absence of beta-hexosaminidase and strage of GM2 gangliodside and related glycolipid. Recently we and others have reported several immunological abnormalities in the CNS.
However, little is known about the mechanism underlying the action of accumulation Gmix as a leading cause for pathological inflammatory responses in the brain. Here we reported that autoantibodies and released-Gmix from apoptotic neuronal cells mediate the nervous inflammation in microglia and astorocytes. The Gmix storage of neuronal cells in SD mice can lead to the release of Gmix from Apoptotic neuronal cells into the extracellular space. The exposure to Gmix can induce the production of TNF-alpha, IL-6 and MIP-1alpha via the Toll-like receptor 4 in the SD mice microglia and astorocytes.Taken together, these results suggest that autoantibodies and released-Gmix may provide to cause nervous inflammatory condition in the brain of SD mice.