Abstract
Background: PDGFβ receptors and their ligand, PDGF-BB, are upregulated in vivo after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is neuroprotective against excitotoxicity and HIV proteins.
Objective: Given this growth factor's neuroprotective ability, we sought to determine if PDGF-BB would be neuroprotective against amyloid-β (1-42), one of the pathological agents associated with Alzheimer's disease (AD).
Methods and Results: In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid-β treatment for 24 h decreased surviving cell number in a concentrationdependent manner. Pretreatment with PDGF-BB failed to provide any neuroprotection against amyloid-β in primary neurons and only very limited protective effects in SH-SY5Y cells. In addition to its neuroprotective action, PDGF promotes cell growth and division in several systems, and the application of PDGFBB alone to serum-starved SH-SY5Y cells resulted in an increase in cell number. Amyloid-β attenuated the mitogenic effects of PDGF-BB, inhibited PDGF-BB-induced PDGFβ receptor phosphorylation, and attenuated the ability of PDGF-BB to protect neurons against NMDA-induced excitotoxicity. Despite the ability of amyloid-β to inhibit PDGFβ receptor activation, immunoprecipitation experiments failed to detect a physical interaction between amyloid-β and PDGF-BB or the PDGFβ receptor. However, G protein-coupled receptor transactivation of the PDGFβ receptor (an exclusively intracellular signaling pathway) remained unaffected by the presence of amyloid-β.
Conclusions: As the PDGF system is upregulated upon neuronal damage, the ability of amyloid-β to inhibit this endogenous neuroprotective system should be further investigated in the context of AD pathophysiology.
Keywords: Amyloid-β, PDGF-BB, PDGFβ receptor, growth factor, neuroprotection, Alzheimer disease.
Current Alzheimer Research
Title:Amyloid-β Inhibits PDGFβ Receptor Activation and Prevents PDGF-BBInduced Neuroprotection
Volume: 15 Issue: 7
Author(s): Hui Liu, Golam T. Saffi, Maryam S. Vasefi, Youngjik Choi, Jeff S. Kruk, Nawaz Ahmed, Nyasha Gondora, John Mielke, Zoya Leonenko and Michael A. Beazely*
Affiliation:
- The Departments of Biology, University of Waterloo School of Pharmacy, Kitchener, ON, N2G IC5,Canada
Keywords: Amyloid-β, PDGF-BB, PDGFβ receptor, growth factor, neuroprotection, Alzheimer disease.
Abstract: Background: PDGFβ receptors and their ligand, PDGF-BB, are upregulated in vivo after neuronal insults such as ischemia. When applied exogenously, PDGF-BB is neuroprotective against excitotoxicity and HIV proteins.
Objective: Given this growth factor's neuroprotective ability, we sought to determine if PDGF-BB would be neuroprotective against amyloid-β (1-42), one of the pathological agents associated with Alzheimer's disease (AD).
Methods and Results: In both primary hippocampal neurons and the human-derived neuroblastoma cell line, SH-SY5Y, amyloid-β treatment for 24 h decreased surviving cell number in a concentrationdependent manner. Pretreatment with PDGF-BB failed to provide any neuroprotection against amyloid-β in primary neurons and only very limited protective effects in SH-SY5Y cells. In addition to its neuroprotective action, PDGF promotes cell growth and division in several systems, and the application of PDGFBB alone to serum-starved SH-SY5Y cells resulted in an increase in cell number. Amyloid-β attenuated the mitogenic effects of PDGF-BB, inhibited PDGF-BB-induced PDGFβ receptor phosphorylation, and attenuated the ability of PDGF-BB to protect neurons against NMDA-induced excitotoxicity. Despite the ability of amyloid-β to inhibit PDGFβ receptor activation, immunoprecipitation experiments failed to detect a physical interaction between amyloid-β and PDGF-BB or the PDGFβ receptor. However, G protein-coupled receptor transactivation of the PDGFβ receptor (an exclusively intracellular signaling pathway) remained unaffected by the presence of amyloid-β.
Conclusions: As the PDGF system is upregulated upon neuronal damage, the ability of amyloid-β to inhibit this endogenous neuroprotective system should be further investigated in the context of AD pathophysiology.
Export Options
About this article
Cite this article as:
Liu Hui, Saffi T. Golam, Vasefi S. Maryam , Choi Youngjik, Kruk S. Jeff , Ahmed Nawaz , Gondora Nyasha , Mielke John , Leonenko Zoya and Beazely A. Michael*, Amyloid-β Inhibits PDGFβ Receptor Activation and Prevents PDGF-BBInduced Neuroprotection, Current Alzheimer Research 2018; 15 (7) . https://dx.doi.org/10.2174/1567205015666180110110321
DOI https://dx.doi.org/10.2174/1567205015666180110110321 |
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
-
P-Glycoprotein, but not Multidrug Resistance Protein 4, Plays a Role in the Systemic Clearance of Irinotecan and SN-38 in Mice
Drug Metabolism Letters MicroRNA Polymorphisms, MicroRNA Pharmacogenomics and Cancer Susceptibility
Current Pharmacogenomics and Personalized Medicine Recent Advances in Targeted Anti-Vasculature Therapy: The Neuroblastoma Model
Current Drug Targets Cancer Stem Cells Switch on Tumor Neovascularization
Current Molecular Medicine Inhibition of RET Activated Pathways: Novel Strategies for Therapeutic Intervention in Human Cancers
Current Pharmaceutical Design A High-Throughput Screening Assay for Determining Cellular Levels of Total Tau Protein
Current Alzheimer Research Novel Drugs for Neuroblastoma
Drug Design Reviews - Online (Discontinued) Cell Arrest and Apoptosis Induced by the Next Generation of Vanadium Based Drugs: Action Mechanism to Structure Relation and Future Perspectives
Anti-Cancer Agents in Medicinal Chemistry Plant Defensins and Defensin-Like Peptides - Biological Activities and Biotechnological Applications
Current Pharmaceutical Design α(N)-Heterocyclic Thiosemicarbazones: Iron Chelators that are Promising for Revival of Gallium in Cancer Chemotherapy
Anti-Cancer Agents in Medicinal Chemistry Doing the Puzzle of Steroid Hormone Action: Biological Functions, Physiological and Clinical Significance of Plasma Membrane-Residing Glucocorticoid Recognizing Proteins
Immunology, Endocrine & Metabolic Agents in Medicinal Chemistry (Discontinued) Targeting Ion Channels for New Strategies in Cancer Diagnosis and Therapy
Current Clinical Pharmacology Stem Cells, Cancer, Liver, and Liver Cancer Stem Cells: Finding a Way Out of the Labyrinth...
Current Cancer Drug Targets Effect of PSEN1 mutations on MAPT methylation in early-onset Alzheimer’s disease
Current Alzheimer Research Half a Century of l-DOPA
Current Topics in Medicinal Chemistry Positron Emission Tomography Imaging of Tumor Hypoxia
Current Medical Imaging Lipid Nanoparticles to Deliver miRNA in Cancer
Current Pharmaceutical Biotechnology Molecular Basis for the Neuroprotective Properties of FKBP-Binding Immunophilin Ligands
Current Medicinal Chemistry - Central Nervous System Agents Modulation of MicroRNAs by <i>Euphorbia Microsciadia</i> Boiss in MDA-MB-231 Cell Line: New Possibilities in Breast Cancer Therapy
Recent Patents on Anti-Cancer Drug Discovery Prolactin Protects Against the Methamphetamine-Induced Cerebral Vascular Toxicity
Current Neurovascular Research