Wakabayashi Masaki, Matsuzaki Katsumi
Graduate School of Pharmaceutical Sciences, Kyoto University, Sakyo-ku, Kyoto, Japan.
FEBS Lett. 2009 Sep 3;583(17):2854-8. doi: 10.1016/j.febslet.2009.07.044. Epub 2009 Aug 3.
Human islet amyloid polypeptide (hIAPP) is the primary component of the amyloid deposits found in the pancreatic islets of patients with type 2 diabetes mellitus. However, it is unknown how amyloid fibrils are formed in vivo. In this study, we demonstrate that gangliosides play an essential role in the formation of amyloid deposits by hIAPP on plasma membranes. Amyloid fibrils accumulated in ganglioside- and cholesterol-rich microscopic domains ('lipid rafts'). The depletion of gangliosides or cholesterol significantly reduced the amount of amyloid deposited. These results clearly showed that the formation of amyloid fibrils was mediated by gangliosides in lipid rafts.
人胰岛淀粉样多肽（hIAPP）是2型糖尿病患者胰岛中淀粉样沉积物的主要成分。然而，目前尚不清楚淀粉样纤维在体内是如何形成的。在本研究中，我们证明神经节苷脂在hIAPP在质膜上形成淀粉样沉积物的过程中起着至关重要的作用。淀粉样纤维聚集在富含神经节苷脂和胆固醇的微小区域（“脂筏”）中。神经节苷脂或胆固醇的耗尽显著减少了淀粉样沉积物的数量。这些结果清楚地表明，淀粉样纤维的形成是由脂筏中的神经节苷脂介导的。
