Abstract
One of the earliest manifestations of Alzheimers disease (AD) is the characteristic inability of affected individuals to form new memories. Memory impairment appears to significantly predate the death of nerve cells, implying that neuronal dysfunction is responsible for the pathophysiology of early stage AD. Mounting evidence now indicates that soluble oligomers of the amyloid-β peptide (Aβ) are the main neurotoxins that lead to early neuronal dysfunction and memory deficits in AD. Cyclic AMP (cAMP) is a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Among other actions, cAMP triggers the phosphorylation and activation of the cAMP responsive element binding protein (CREB), a transcription factor that regulates the expression of genes that are important for long-term memory. Here, we discuss recent evidence suggesting that cAMP enhancing compounds may find applications as neurocognitive enhancers in AD and in other neurological disorders, as well as possible roles of cAMP in the regulation of neuronal regeneration. In particular, we review recent results showing that low concentrations of 2,4-dinitrophenol (DNP) upregulate neuronal cAMP and tau levels, promote neurite outgrowth and neuronal differentiation and block the oligomerization and neurotoxicity of Aβ. Possible implications of these findings in the development of novel therapeutic approaches in AD are discussed.
Keywords: 2,4-dinitrophenol, cAMP responsive element binding protein, Neuritogenesis, brain-derived neurotrophic factor, cortical neuronal, PKA levels
Current Alzheimer Research
Title: Cyclic AMP Enhancers and Aβ Oligomerization Blockers as Potential Therapeutic Agents in Alzheimers Disease
Volume: 4 Issue: 3
Author(s): Fernanda G. De Felice, Ana Paula Wasilewska-Sampaio, Anna Carolina A. P. Barbosa, Flavia C.A. Gomes and Sergio T. Ferreira
Affiliation:
Keywords: 2,4-dinitrophenol, cAMP responsive element binding protein, Neuritogenesis, brain-derived neurotrophic factor, cortical neuronal, PKA levels
Abstract: One of the earliest manifestations of Alzheimers disease (AD) is the characteristic inability of affected individuals to form new memories. Memory impairment appears to significantly predate the death of nerve cells, implying that neuronal dysfunction is responsible for the pathophysiology of early stage AD. Mounting evidence now indicates that soluble oligomers of the amyloid-β peptide (Aβ) are the main neurotoxins that lead to early neuronal dysfunction and memory deficits in AD. Cyclic AMP (cAMP) is a central component of intracellular signaling pathways that regulate a wide range of biological functions, including memory. Among other actions, cAMP triggers the phosphorylation and activation of the cAMP responsive element binding protein (CREB), a transcription factor that regulates the expression of genes that are important for long-term memory. Here, we discuss recent evidence suggesting that cAMP enhancing compounds may find applications as neurocognitive enhancers in AD and in other neurological disorders, as well as possible roles of cAMP in the regulation of neuronal regeneration. In particular, we review recent results showing that low concentrations of 2,4-dinitrophenol (DNP) upregulate neuronal cAMP and tau levels, promote neurite outgrowth and neuronal differentiation and block the oligomerization and neurotoxicity of Aβ. Possible implications of these findings in the development of novel therapeutic approaches in AD are discussed.
Export Options
About this article
Cite this article as:
Fernanda G. De Felice , Ana Paula Wasilewska-Sampaio , Anna Carolina A. P. Barbosa , Flavia C.A. Gomes and Sergio T. Ferreira , Cyclic AMP Enhancers and Aβ Oligomerization Blockers as Potential Therapeutic Agents in Alzheimers Disease, Current Alzheimer Research 2007; 4 (3) . https://dx.doi.org/10.2174/156720507781077287
DOI https://dx.doi.org/10.2174/156720507781077287 |
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
Alzheimer's Disease Drug Development
Alzheimer's disease is a progressive neurodegenerative disorder that affects millions of people worldwide. Despite decades of research, no cure or disease-modifying treatment is available yet. Therefore, the need for developing effective therapies to treat Alzheimer's disease is an urgent matter. This special issue aims to provide a comprehensive overview of ...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
- 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
-
Diagnosis, Pathogenesis and Therapeutic Targets in Amyotrophic Lateral Sclerosis
CNS & Neurological Disorders - Drug Targets Cytotoxic and Anticancer Activities of Isatin and Its Derivatives: A Comprehensive Review from 2000-2008
Anti-Cancer Agents in Medicinal Chemistry Choline Kinase: An Important Target for Cancer
Current Medicinal Chemistry Biochemical Characterization of Apoptotic Cleavage of KH-Type Splicing Regulatory Protein (KSRP) / Far Upstream Element-Binding Protein 2 (FBP2)
Protein & Peptide Letters Clinical Importance and Potential Use of Small Molecule Inhibitors of Focal Adhesion Kinase
Anti-Cancer Agents in Medicinal Chemistry The Role of Stem Cells in Muscular Dystrophies
Current Gene Therapy A Novel Tetradentate Ruthenium(II) Complex Containing Tris(2- pyridylmethyl)amine (tpa) as an Inhibitor of Beta-Amyloid Fibrillation
Current Alzheimer Research Diagnostics, Prognostic and Therapeutic Exploitation of Telomeres and Telomerase in Leukemias
Current Pharmaceutical Biotechnology New Approaches to Target Cancer Stem Cells: Current Scenario
Mini-Reviews in Medicinal Chemistry Specific Recognition of DNA by Small Molecules
Current Medicinal Chemistry Development of Anti-HIV Agents Targeting Dynamic Supramolecular Mechanism: Entry and Fusion Inhibitors Based on CXCR4/CCR5 Antagonists and gp41-C34-Remodeling Peptides
Current HIV Research Therapy in Prion Diseases: From Molecular and Cellular Biology to Therapeutic Targets
Infectious Disorders - Drug Targets Neurodegenerative Diseases and Flavonoids: Special Reference to Kaempferol
CNS & Neurological Disorders - Drug Targets The Impact of Small Heat Shock Proteins (HspBs) in Alzheimer’s and Other Neurological Diseases
Current Pharmaceutical Design New Preparative Approaches for Micro and Nano Drug Delivery Carriers
Current Drug Delivery From Protein to Peptides: a Spectrum of Non-Hydrolytic Functions of Acetylcholinesterase
Protein & Peptide Letters Effect of Oil Extract from Microalgae (<i>Schizochytrium</i> sp.) on the Viability and Apoptosis of Human Osteosarcoma Cells
Current Pharmaceutical Biotechnology Immunophilins: Structures, Mechanisms and Ligands
Current Molecular Pharmacology Insulin Modulates <i>In Vitro Secretion</i> of Cytokines and Cytotoxins by Human Glial Cells
Current Alzheimer Research HSP60 as a Drug Target
Current Pharmaceutical Design