抑制ANGPTL8可以通过减少通过PirB信号通路的突触损失来防止与糖尿病相关的认知功能障碍

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Xiaoyu Meng^1,2, Danpei Li^1,2, Ranran Kan^1,2

¹Division of Endocrinology, Department of Internal Medicine, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China.

Journal of neuroinflammation

|August 2, 2024

概括

2型糖尿病与认知能力下降有关. 这项研究揭示了血管类蛋白8 (ANGPTL8) 通过PirB受体驱动这种功能障碍,提供了一个新的治疗点.

科学领域:

神经科学是一个神经科学.
内分泌学在内分泌学.
病理学病理学病理学

背景情况:

2型糖尿病 (T2D) 是认知功能障碍的重要危险因素.
抗胰岛素类蛋白8 (ANGPTL8) 在糖尿病相关认知功能障碍中的作用目前尚不清楚.
这项研究研究了ANGPTL8-PirB途径在中枢神经系统在T2D认知障碍中的作用.

研究的目的:

阐明ANGPTL8在糖尿病相关认知功能障碍的发病过程中的作用.
探索ANGPTL8与中枢神经系统中的配对免疫球蛋白类受体B (PirB) 之间的相互作用.
确定管理T2D认知衰退的潜在治疗点.

主要方法:

测量了T2D患者的ANGPTL8水平与对照对比的认知功能障碍.
利用T2D的小鼠模型来评估认知功能 (巴恩斯迷宫,新型物体识别) 和分子标记.
研究了重组ANGPTL8对初级神经元和微质细胞的影响,包括PirB通路抑制和中枢神经系统特异性基因淘汰.

主要成果:

由海马神经元分泌的ANGPTL8有助于神经炎症和糖尿病人大脑中的突触可塑性受损.
Angptl8的神经元特异性淘汰改善了与糖尿病相关的认知功能障碍和神经炎症.
ANGPTL8通过PirB下调的突触标记物和上调的微质前炎性细胞因子发出信号,PirB淘汰小鼠表现出耐药性.

结论:

ANGPTL8在糖尿病相关认知功能障碍的发展中起着至关重要的作用.
ANGPTL8-PirB信号通路与T2D中神经炎症和突触损伤有关.
准ANGPTL8-PirB通路为T2D认知障碍提供了一个有前途的治疗策略.

关键词:

类似于 ангиопоетин的蛋白质 8 糖尿病相关的认知功能障碍微质细胞中的微质细胞这些神经元是神经元.配对的免疫球蛋白类受体B受体

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