Abstract
The soluble amyloid β precursor protein α (sAβPPα) released after α-secretase cleavage of the amyloid β precursor protein (AβPP) has several functions including modulation of neuronal excitability and synaptic plasticity; it has been suggested that some of these effects are mediated by activation of NF-κB via induction of PI3K/Akt signaling pathway.
We have recently described the presence of several consensus binding sites of c-Rel transcription factor in the promoter region of the GNB2L1 gene, coding for the Receptor for Activated C Kinase -1 (RACK-1). We investigated whether sAβPPα could influence the expression of RACK-1 through NF-κB involvement. Our data demonstrate that sAβPPα regulates RACK-1 gene expression through PI3K/Akt-dependent pathway, inducing c-Rel nuclear translocation and NF-κB activation. Since RACK-1 is the scaffold of protein kinase C βII (PKCβII), we turned our attention to this kinase in order to evaluate whether sAβPPα could also influence PKCβII signalling demonstrating that sAβPPα induces PKCβII translocation and interaction with its scaffold with consequent RACK-1/PKCβII complex increase in membrane. Altogether these results suggest the existence of an interesting loop between the functions of the metabolic products of AβPP and the role of PKC and that the impact of a dysregulated AβPP metabolism occurring in several conditions (from physiological aging to injury response) may have consequences on the potential protective functions of the non amyloidogenic sAβPPα.
Keywords: sAPPα, PI3K-Akt, NF-κB, RACK-1, signal transduction, protein kinase C βII.
Current Alzheimer Research
Title:Modulation of Rack-1/PKCβII Signalling By Soluble AβPPα in SH-SY5Y Cells
Volume: 10 Issue: 7
Author(s): Erica Buoso, Fabrizio Biundo, Cristina Lanni, Stefania Aiello, Serena Grossi, Gennaro Schettini, Stefano Govoni and Marco Racchi
Affiliation:
Keywords: sAPPα, PI3K-Akt, NF-κB, RACK-1, signal transduction, protein kinase C βII.
Abstract: The soluble amyloid β precursor protein α (sAβPPα) released after α-secretase cleavage of the amyloid β precursor protein (AβPP) has several functions including modulation of neuronal excitability and synaptic plasticity; it has been suggested that some of these effects are mediated by activation of NF-κB via induction of PI3K/Akt signaling pathway.
We have recently described the presence of several consensus binding sites of c-Rel transcription factor in the promoter region of the GNB2L1 gene, coding for the Receptor for Activated C Kinase -1 (RACK-1). We investigated whether sAβPPα could influence the expression of RACK-1 through NF-κB involvement. Our data demonstrate that sAβPPα regulates RACK-1 gene expression through PI3K/Akt-dependent pathway, inducing c-Rel nuclear translocation and NF-κB activation. Since RACK-1 is the scaffold of protein kinase C βII (PKCβII), we turned our attention to this kinase in order to evaluate whether sAβPPα could also influence PKCβII signalling demonstrating that sAβPPα induces PKCβII translocation and interaction with its scaffold with consequent RACK-1/PKCβII complex increase in membrane. Altogether these results suggest the existence of an interesting loop between the functions of the metabolic products of AβPP and the role of PKC and that the impact of a dysregulated AβPP metabolism occurring in several conditions (from physiological aging to injury response) may have consequences on the potential protective functions of the non amyloidogenic sAβPPα.
Export Options
About this article
Cite this article as:
Buoso Erica, Biundo Fabrizio, Lanni Cristina, Aiello Stefania, Grossi Serena, Schettini Gennaro, Govoni Stefano and Racchi Marco, Modulation of Rack-1/PKCβII Signalling By Soluble AβPPα in SH-SY5Y Cells, Current Alzheimer Research 2013; 10 (7) . https://dx.doi.org/10.2174/15672050113109990145
DOI https://dx.doi.org/10.2174/15672050113109990145 |
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
-
Pathophysiology, Diagnosis and Clinical Management of Hepatorenal Syndrome: From Classic to New Drugs
Current Vascular Pharmacology Mineralocorticoid Receptor Antagonism and Cardiac Remodeling in Ischemic Heart Failure
Current Medicinal Chemistry - Cardiovascular & Hematological Agents Natural Products to Anti-trypanosomal Drugs: An Overview of New Drug Prototypes for American Trypanosomiasis
Cardiovascular & Hematological Agents in Medicinal Chemistry Role of Oxidative-Nitrosative Stress and Downstream Pathways in Various Forms of Cardiomyopathy and Heart Failure
Current Vascular Pharmacology Prevalence of Dilated Cardiomyopathy in HIV-Infected African Patients Not Receiving HAART: A Multicenter, Observational, Prospective, Cohort Study in Rwanda
Current HIV Research The Role of Myocardial Collagen Network in Hypertensive Heart Disease
Current Hypertension Reviews Cell Immunity in Coronary Artery Disease (CAD)
Current Immunology Reviews (Discontinued) Serum Collagen Markers and Heart Failure
Cardiovascular & Hematological Disorders-Drug Targets Caveolae and Caveolin-1: Novel Potential Targets for the Treatment of Cardiovascular Disease
Current Pharmaceutical Design Sildenafil and Cardioprotection
Current Pharmaceutical Design GDF 15 - A Novel Biomarker in the Offing for Heart Failure
Current Cardiology Reviews Meet Our Editor:
Current Cardiology Reviews A Review of Sirt1 and Sirt1 Modulators in Cardiovascular and Metabolic Diseases
Recent Patents on Cardiovascular Drug Discovery Advanced Glycation End Products: A Link Between Periodontitis and Diabetes Mellitus?
Current Diabetes Reviews MicroRNA Regulation and Role in Stem Cell Maintenance, Cardiac Differentiation and Hypertrophy
Current Molecular Medicine The Importance of Lost Minerals in Heart Failure
Cardiovascular & Hematological Agents in Medicinal Chemistry The Wnt/β-catenin Signalling Pathway Inhibitor Sclerostin is a Biomarker for Early Atherosclerosis in Obesity
Current Neurovascular Research Risk Factors for Development of Heart Failure
Current Cardiology Reviews Peripartum Cardiomyopathy: An Intensivist's Perspective
Current Women`s Health Reviews Current and Future Chemotherapy for Chagas Disease
Current Medicinal Chemistry