Abstract
We have examined the anti-angiogenic compound, angiostatin as a modulator of inflammatory reactivity and vascular responses and for neuroprotection in an animal model of Alzheimer’s disease (AD). Intra-hippocampal amyloidbeta (Aβ1-42) injection, relative to controls phosphate buffer saline (PBS) or reverse peptide Aβ42-1, increased gliosis in the molecular layer (ML) of rat hippocampus. Vascular remodeling was indicated from increased microvessel immunoreactivity (ir) in ML suggesting the possibility of an angiogenic response to peptide injection. Administration of Aβ1-42 also induced a loss of neurons in the granule cell region of hippocampus relative to controls. Treatment of peptide-injected rats with angiostatin was associated with a spectrum of modulatory effects including reduced microgliosis (by 34%), diminished microvessel ir (by 36%) and increased neuronal viability (by 31%) compared with peptide injection alone. Angiostatin treatment was ineffective in reducing astrogliosis induced by Aβ1-42 and applied alone the compound had no significant effect to alter gliosis, microvessel ir or neuronal viability compared with PBS control. In vitro, angiostatin significantly attenuated secretion of the pro-angiogenic agent, vascular endothelial growth factor (VEGF) in lipopolysaccharide (LPS)-stimulated THP-1 cells. Our findings provide novel evidence for a broad spectrum of angiostatin effects in an animal model of AD including actions to reduce inflammatory reactivity, stabilize vascular remodeling and confer neuroprotection. The overall effects of angiostatin are consistent with actions of the compound to inhibit microglial secretion of VEGF.
Keywords: AD animal model, intrahippocampal injection of Aβ1-42, microgliosis, vascular perturbations, angiostatin, antiangiogenic, vascular endothelial growth factor, immunohistochemistry
Current Alzheimer Research
Title:Actions of the Anti-Angiogenic Compound Angiostatin in an Animal Model of Alzheimer’s Disease
Volume: 10 Issue: 3
Author(s): Jae K Ryu, Jonathan P Little, Andis Klegeris, Nattinee Jantaratnotai and James G McLarnon
Affiliation:
Keywords: AD animal model, intrahippocampal injection of Aβ1-42, microgliosis, vascular perturbations, angiostatin, antiangiogenic, vascular endothelial growth factor, immunohistochemistry
Abstract: We have examined the anti-angiogenic compound, angiostatin as a modulator of inflammatory reactivity and vascular responses and for neuroprotection in an animal model of Alzheimer’s disease (AD). Intra-hippocampal amyloidbeta (Aβ1-42) injection, relative to controls phosphate buffer saline (PBS) or reverse peptide Aβ42-1, increased gliosis in the molecular layer (ML) of rat hippocampus. Vascular remodeling was indicated from increased microvessel immunoreactivity (ir) in ML suggesting the possibility of an angiogenic response to peptide injection. Administration of Aβ1-42 also induced a loss of neurons in the granule cell region of hippocampus relative to controls. Treatment of peptide-injected rats with angiostatin was associated with a spectrum of modulatory effects including reduced microgliosis (by 34%), diminished microvessel ir (by 36%) and increased neuronal viability (by 31%) compared with peptide injection alone. Angiostatin treatment was ineffective in reducing astrogliosis induced by Aβ1-42 and applied alone the compound had no significant effect to alter gliosis, microvessel ir or neuronal viability compared with PBS control. In vitro, angiostatin significantly attenuated secretion of the pro-angiogenic agent, vascular endothelial growth factor (VEGF) in lipopolysaccharide (LPS)-stimulated THP-1 cells. Our findings provide novel evidence for a broad spectrum of angiostatin effects in an animal model of AD including actions to reduce inflammatory reactivity, stabilize vascular remodeling and confer neuroprotection. The overall effects of angiostatin are consistent with actions of the compound to inhibit microglial secretion of VEGF.
Export Options
About this article
Cite this article as:
K Ryu Jae, P Little Jonathan, Klegeris Andis, Jantaratnotai Nattinee and G McLarnon James, Actions of the Anti-Angiogenic Compound Angiostatin in an Animal Model of Alzheimer’s Disease, Current Alzheimer Research 2013; 10 (3) . https://dx.doi.org/10.2174/1567205011310030004
DOI https://dx.doi.org/10.2174/1567205011310030004 |
Print ISSN 1567-2050 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5828 |
Call for Papers in Thematic Issues
New Advances in the Prevention, Diagnosis, Treatment, and Rehabilitation of Alzheimer's Disease
Aims and Scope: Introduction: Alzheimer's disease (AD) poses a significant global health challenge, with an increasing prevalence that demands concerted efforts to advance our understanding and strategies for prevention, diagnosis, treatment, and rehabilitation. This thematic issue aims to bring together cutting-edge research and innovative approaches from multidisciplinary perspectives to address ...read more
Current updates on the Role of Neuroinflammation in Neurodegenerative Disorders
Neuroinflammation is an invariable hallmark of chronic and acute neurodegenerative disorders and has long been considered a potential drug target for Alzheimer?s disease (AD) and dementia. Significant evidence of inflammatory processes as a feature of AD is provided by the presence of inflammatory markers in plasma, CSF and postmortem brain ...read more
Deep Learning for Advancing Alzheimer's Disease Research
Alzheimer's disease (AD) poses a significant global health challenge, with an increasing number of individuals affected yearly. Deep learning, a subfield of artificial intelligence, has shown immense potential in various domains, including healthcare. This thematic issue of Current Alzheimer Research explores the application of deep learning techniques in advancing our ...read more
Diagnostic and therapeutic biomarkers of dementia
Dementia affects 18 million people worldwide. Dementia is a syndrome of symptoms caused by brain disease, usually chronic or progressive, clinically characterized by multiple impairments of higher cortical functions such as memory, thinking, orientation, and learning. In addition, in the course of dementia, cognitive deficits are observed, which often hinder ...read more
- Author Guidelines
- Graphical Abstracts
- Fabricating and Stating False Information
- Research Misconduct
- Post Publication Discussions and Corrections
- Publishing Ethics and Rectitude
- Increase Visibility of Your Article
- Archiving Policies
- Peer Review Workflow
- Order Your Article Before Print
- Promote Your Article
- Manuscript Transfer Facility
- Editorial Policies
- Allegations from Whistleblowers
- Announcements
Related Articles
-
RAGE: A Multi-Ligand Receptor Unveiling Novel Insights in Health and Disease
Current Medicinal Chemistry The Evolving Landscape in the Development of Isocitrate Dehydrogenase Mutant Inhibitors
Mini-Reviews in Medicinal Chemistry Nucleic Acid Aptamers as Novel Class of Therapeutics to Mitigate Alzheimer’s Disease Pathology
Current Alzheimer Research Self-Assembled Micelles of Amphiphilic PEGylated Drugs for Cancer Treatment
Current Drug Targets Mitocans: Mitochondrial Targeted Anti-Cancer Drugs as Improved Therapies and Related Patent Documents
Recent Patents on Anti-Cancer Drug Discovery Meet Our Editorial Board Member
Current Medicinal Chemistry Glycogen Synthase Kinase 3 as an Anticancer Drug Target: Novel Experimental Findings and Trends in the Design of Inhibitors
Current Pharmaceutical Design Nanotechnology and Radiopharmaceuticals: Diagnostic and Therapeutic Approaches
Current Drug Delivery State of Research Tracks and Property Protection of Photodynamic Sensitizers and Delivery Methodologies
Recent Patents on Chemical Engineering Research Highlights BAY 1436032: A Novel Pan-mutant IDH1 Inhibitor Extends Survival of Mice with Experimental Brain Tumors
CNS & Neurological Disorders - Drug Targets Targeting Calcium Channels to Block Tumor Vascularization
Recent Patents on Anti-Cancer Drug Discovery Engineered Exosomes: A Promising Drug Delivery Strategy for Brain Diseases
Current Medicinal Chemistry Chitinases: Biomarkers for Human Diseases
Protein & Peptide Letters Prospects of Bacteriotherapy with Nanotechnology in Nanoparticledrug Conjugation Approach for Cancer Therapy
Current Medicinal Chemistry Natural and Engineered Cystine Knot Miniproteins for Diagnostic and Therapeutic Applications
Current Pharmaceutical Design Nucleic Acid Aptamers Against Protein Kinases
Current Medicinal Chemistry Efficacy and Safety of Combined Radiotherapy with EGFR Inhibitors and Chemotherapy for Laryngeal Organ Preservation in Patients with Locally Advanced Hypopharyngeal Carcinomas
Current Cancer Drug Targets Delivery of Large Genomic DNA Inserts > 100 kb Using HSV-1 Amplicons
Current Gene Therapy Clinical Experience with Antiangiogenic Therapy in Leukemia
Current Cancer Drug Targets Anticancer Mechanisms of Bioactive Peptides
Protein & Peptide Letters