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C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer’s Disease Model Associated with Vascular Dysfunction

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 ce...

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Autores principales: Fu, Xiaoxiao, Wang, Jing, Cai, Huaying, Jiang, Hong, Han, Shu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025163/
https://www.ncbi.nlm.nih.gov/pubmed/35455468
http://dx.doi.org/10.3390/ph15040471
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author Fu, Xiaoxiao
Wang, Jing
Cai, Huaying
Jiang, Hong
Han, Shu
author_facet Fu, Xiaoxiao
Wang, Jing
Cai, Huaying
Jiang, Hong
Han, Shu
author_sort Fu, Xiaoxiao
collection PubMed
description 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.
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spelling pubmed-90251632022-04-23 C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer’s Disease Model Associated with Vascular Dysfunction Fu, Xiaoxiao Wang, Jing Cai, Huaying Jiang, Hong Han, Shu Pharmaceuticals (Basel) Article 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. MDPI 2022-04-13 /pmc/articles/PMC9025163/ /pubmed/35455468 http://dx.doi.org/10.3390/ph15040471 Text en © 2022 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Fu, Xiaoxiao
Wang, Jing
Cai, Huaying
Jiang, Hong
Han, Shu
C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer’s Disease Model Associated with Vascular Dysfunction
title C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer’s Disease Model Associated with Vascular Dysfunction
title_full C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer’s Disease Model Associated with Vascular Dysfunction
title_fullStr C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer’s Disease Model Associated with Vascular Dysfunction
title_full_unstemmed C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer’s Disease Model Associated with Vascular Dysfunction
title_short C16 Peptide and Ang-1 Improve Functional Disability and Pathological Changes in an Alzheimer’s Disease Model Associated with Vascular Dysfunction
title_sort c16 peptide and ang-1 improve functional disability and pathological changes in an alzheimer’s disease model associated with vascular dysfunction
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9025163/
https://www.ncbi.nlm.nih.gov/pubmed/35455468
http://dx.doi.org/10.3390/ph15040471
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