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.
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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 |
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