C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer's Disease Model Associated with Vascular Dysfunction.
C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer's Disease Model Associated with Vascular Dysfunction.
复制标题
DOI：
10.3390/ph15040471
复制
发表时间：
2022-04-13
期刊：
影响因子：
--
通讯作者：
中科院分区：
文献类型：
--
作者：
阿尔茨海默病（AD）是一种以神经元细胞死亡、tau蛋白病理和过度炎症反应为特征的神经系统疾病。多种血管危险因素导致血脑屏障（BBB）损伤，继发性血管渗漏，炎症细胞浸润，加重AD的功能障碍和病理改变。生长因子血管生成素-1 （ang1）通过与受体酪氨酸激酶2 （Tie2）结合，稳定内皮，降低内皮通透性。C16肽（KAFDITYVRLKF）选择性结合整合素ανβ3，并通过干扰白细胞配体竞争性地抑制白细胞向中枢神经系统的转运。本研究选取雄性SD大鼠45只，随机分为三组：载药组、C16肽+ Ang1 （C + A）组和假对照组。对照组和C + A组采用双血管闭塞（2-VO）联合动脉结扎，然后向海马内注射Aβ1-42。假对照组接受假手术并注射等量的磷酸盐缓冲盐水（PBS）代替Aβ1-42。C + A组给予含C16 2 mg、Ang-1 400µg的药物1 mL，每日2周。假对照组和载药组给予PBS 1 mL，持续2周。我们的研究结果表明，ang1 + C16治疗通过抑制炎症细胞浸润、保护血管内皮细胞和维持血脑屏障通透性来改善功能障碍和减少神经元死亡。结果表明，这些化合物可能是潜在的治疗阿尔茨海默病的药物，值得进一步研究。
Alzheimer’s disease (AD) is a neurological disorder characterized by neuronal cell death, tau pathology, and excessive inflammatory responses. Several vascular risk factors contribute to damage of the blood–brain barrier (BBB), secondary leak-out of blood vessels, and infiltration of inflammatory cells, which aggravate the functional disability and pathological changes in AD. Growth factor angiopoietin-1 (Ang-1) can stabilize the endothelium and reduce endothelial permeability by binding to receptor tyrosine kinase 2 (Tie2). C16 peptide (KAFDITYVRLKF) selectively binds to integrin ανβ3 and competitively inhibits leukocyte transmigration into the central nervous system by interfering with leukocyte ligands. In the present study, 45 male Sprague-Dawley (SD) rats were randomly divided into three groups: vehicle group, C16 peptide + Ang1 (C + A) group, and sham control group. The vehicle and C + A groups were subjected to two-vessel occlusion (2-VO) with artery ligation followed by Aβ1-42 injection into the hippocampus. The sham control group underwent sham surgery and injection with an equal amount of phosphate-buffered saline (PBS) instead of Aβ1-42. The C + A group was administered 1 mL of drug containing 2 mg of C16 and 400 µg of Ang-1 daily for 2 weeks. The sham control and vehicle groups were administered 1 mL of PBS for 2 weeks. Our results showed that treatment with Ang-1 plus C16 improved functional disability and reduced neuronal death by inhibiting inflammatory cell infiltration, protecting vascular endothelial cells, and maintaining BBB permeability. The results suggest that these compounds may be potential therapeutic agents for AD and warrant further investigation.
登录
查看更多内容
影响因子：
4.8
作者：
Michalicova A;Majerova P;Kovac A
通讯作者：
Kovac A
加兰他敏改善小鼠认知、海马炎症和脂多糖引起的突触可塑性损伤
影响因子：
9.3
作者：
Liu Y;Zhang Y;Zheng X;Fang T;Yang X;Luo X;Guo A;Newell KA;Huang XF;Yu Y
通讯作者：
Yu Y
影响因子：
16.6
作者：
Iturria-Medina Y;Sotero RC;Toussaint PJ;Mateos-Pérez JM;Evans AC;Alzheimer’s Disease Neuroimaging Initiative
通讯作者：
Alzheimer’s Disease Neuroimaging Initiative
DOI：
10.1038/nrneurol.2017.188
发表时间：
2018-03
期刊：
Nature reviews. Neurology
影响因子：
--
作者：
Sweeney MD;Sagare AP;Zlokovic BV
通讯作者：
Zlokovic BV
影响因子：
2
作者：
Kim, Min Soo;Yu, Jung Min;Joo, Seong Soo
通讯作者：
Joo, Seong Soo