Chloroquine-induced endocytic pathway abnormalities: Cellular model of GM1 ganglioside-induced Abeta fibrillogenesis in Alzheimer's disease |
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Authors: | Yuyama Kohei Yamamoto Naoki Yanagisawa Katsuhiko |
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Institution: | Department of Alzheimer's Disease Research, National Institute for Longevity Sciences, National Center for Geriatrics and Gerontology, 36-3 Gengo, Morioka, Obu 474-8522, Japan. |
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Abstract: | Endocytic pathway abnormalities were previously observed in brains affected with Alzheimer’s disease (AD). To clarify the pathological relevance of these abnormalities to assembly of amyloid β-protein (Aβ), we treated PC12 cells with chloroquine, which potently perturbs membrane trafficking from endosomes to lysosomes. Chloroquine treatment induced accumulation of GM1 ganglioside (GM1) in Rab5-positive enlarged early endosomes and on the cell surface. Notably, an increase in GM1 level on the cell surface was sufficient to induce Aβ assembly. Our results suggest that endocytic pathway abnormalities in AD brain induce GM1 accumulation on the cell surface, leading to amyloid fibril formation in brain. |
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Keywords: | Alzheimer’s disease Amyloid β-protein GM1 ganglioside Endosome Rab5 Chloroquine |
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