アルツハイマー病、他の認知症、老化 Alzheimer's Disease, Other Dementia, Aging

P2-1-196 レプチンは神経細胞膜のGM1ガングリオシド発現減少を介してAβ重合体形成を抑制する Leptin inhibits Aβ fibrillogenesis through suppression of GM1 ganglioside expression on neuronal membranes ○山本直樹1, 谷田守2,3, 祖父江和哉4, 谷浦秀夫1, 鈴木健二1 ○Naoki Yamamoto1, Mamoru Tanida2,3, Kazuya Sobue4, Hideo Taniura1, Kenji Suzuki1 立命館大・薬1, 立命館大・生命科学・生命医科2, 金沢医科大・生理23, 名市大院・医・麻酔4 Dept. Pharmacy, Ritsumeikan Univ., Shiga1, Dept. Life Sciences, Ritsumeikan Univ., Shiga2, Dept. Physiology II, Kanazawa Med. Univ., Ishikawa3, Dept. Anesthesiol., Nagoya City Univ., Aichi4 Leptin is a centrally acting hormone controlling metabolic pathways. Recent epidemiological studies suggest that plasma leptin is protective against AD. However, the mechanisms underlying these effects remain uncertain. To investigate whether leptin inhibit the assembly of amyloid β-protein (Aβ) from the cell surface of neurons, we treated leptin for primary neurons. The leptin treatment induced a decrease in GM1 ganglioside levels in detergent-resistant membrane microdomains (DRMs) of neurons. The leptin-induced effects on GM1 ganglioside levels were inhibited by a phosphatidylinositol 3-kinase inhibitor (LY294002), but not extracellular signal-regulated kinase inhibitor (PD98059). In addition, Rapamycin blocked the induction of GM1 ganglioside expression in DRMs by leptin. Furthermore, assembly of amyloid β-protein in cultures of neurons was significantly decreased by pre-treatment of leptin. These results suggest that leptin inhibits amyloid β-protein assembly by decreasing GM1 ganglioside expression in neuronal membrane.

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