Mi Xue, Ruan Xinglin, Lin Renyi, Huang Shuxin, Cai Ping, Chen Xiaochun, Liao Jiangfeng, Dai Xiaoman
Public Technology Service Center, Fujian Medical University, Fuzhou, China.
Fujian Key Laboratory of Molecular Neurology, Institute of Neuroscience, Fujian Medical University, Fuzhou, China.
Front Pharmacol. 2025 Jul 4;16:1572771. doi: 10.3389/fphar.2025.1572771. eCollection 2025.
BACKGROUND/OBJECTIVES: Although Alzheimer's disease (AD) is the most prevalent dementia in late life, with amyloid beta (Aβ) deposition and neuroinflammation are recognized among its primary pathological features. Currently, there is currently still a lack of effective therapeutic drugs for AD. () is abundant in active ingredients that harbor anti-inflammatory properties in both central nervous system and the periphery. We attempted to determine whether contained exosome-like nanovesicles (GLENVs) and whether these GLENVs can alleviate cognitive impairment.
We extracted GLENVs by the differential ultracentrifugation method and identified the components by liquid chromatography-mass spectrometry (LC-MS). The 5×FAD mice underwent a 3-month intranasal administration of GLENVs and their behavioral and pathological changes were evaluated.
GLENVs were successfully extracted and identified to contain multiple ganoderic acids; intranasal administration allowed GLENVs to penetrate the blood-brain barrier to exert their effects directly. The 3-month GLENVs treatment effectively ameliorated the impairment in the memory and learning of the 5×FAD mice. The GLENVs treatment also reduced Aβ deposition in the cortex and hippocampus of 5×FAD mice, overactivated microglia, reactive astrocytes, and pro-inflammatory factors, and inhibited the Janus kinase 2 (JAK2)/Signal transducer and activator of transcription 3 (STAT3) signaling pathway. Moreover, GLENVs exerted no adverse effects on liver and kidney function.
GLENVs may be a promising candidate for AD treatment.
背景/目的：尽管阿尔茨海默病（AD）是老年期最常见的痴呆症，淀粉样β蛋白（Aβ）沉积和神经炎症是其主要病理特征。目前，AD仍缺乏有效的治疗药物。（）富含在中枢神经系统和外周均具有抗炎特性的活性成分。我们试图确定（）是否含有类外泌体纳米囊泡（GLENVs）以及这些GLENVs是否能减轻认知障碍。
我们通过差速超速离心法提取GLENVs，并通过液相色谱 - 质谱联用（LC - MS）鉴定其成分。对5×FAD小鼠进行为期3个月的GLENVs鼻内给药，并评估其行为和病理变化。
成功提取并鉴定出GLENVs含有多种灵芝酸；鼻内给药使GLENVs能够穿透血脑屏障直接发挥作用。为期3个月的GLENVs治疗有效改善了5×FAD小鼠的记忆和学习障碍。GLENVs治疗还减少了5×FAD小鼠皮质和海马中的Aβ沉积、过度活化的小胶质细胞、反应性星形胶质细胞和促炎因子，并抑制了Janus激酶2（JAK2）/信号转导子和转录激活子3（STAT3）信号通路。此外，GLENVs对肝肾功能无不良影响。
GLENVs可能是一种有前景的AD治疗候选物。
