Abstract
Alzheimers disease (AD) is a late-life cognitive disorder associated, among other things, to the presence of extracellular aggregates of fibrillar amyloid beta protein (Aβ). However, there is growing evidence that early stages of AD may be due to neuronal network dysfunction produced by the actions of soluble forms of Aβ. Therefore, the development of new therapeutic strategies to treat AD, at least during its first stages, may be focused on preventing or reversing, the deleterious effects that soluble Aβ exerts on neuronal circuit function. In order to do so, it is necessary to elucidate the pathophysiological processes involved in Aβ-induced neuronal network dysfunction and the molecular processes underlying such dysfunction. Over the last decades, there has been extensive research about the molecular mechanisms involved in the effects of Aβ as well as possible neuroprotective strategies against such effects. Here we are going to review some of the intracellular pathways triggered by Aβ, which involve membrane receptors such as nicotinic-R, NMDA-R, integrins, TNF-R1, RAGE, FPRL and p75NTR and their intracellular mediators such as GSK3, PKC, PI3K, Akt, FAK, MAPK family, Src family and cdk5. Several of these pathways may constitute therapeutic targets for the treatment of the Aβ-induced neuronal network dysfunction which is, at least in part, the basis for cognitive dysfunction in AD.
Keywords: Alzheimer's disease, Aβ-signaling pathways, neuronal network dysfunction, Aβ-related receptors and pharmacological targets
Mini-Reviews in Medicinal Chemistry
Title: Pharmacology of the Intracellular Pathways Activated by Amyloid Beta Protein
Volume: 9 Issue: 6
Author(s): Hugo Balleza-Tapia and Fernando Pena
Affiliation:
Keywords: Alzheimer's disease, Aβ-signaling pathways, neuronal network dysfunction, Aβ-related receptors and pharmacological targets
Abstract: Alzheimers disease (AD) is a late-life cognitive disorder associated, among other things, to the presence of extracellular aggregates of fibrillar amyloid beta protein (Aβ). However, there is growing evidence that early stages of AD may be due to neuronal network dysfunction produced by the actions of soluble forms of Aβ. Therefore, the development of new therapeutic strategies to treat AD, at least during its first stages, may be focused on preventing or reversing, the deleterious effects that soluble Aβ exerts on neuronal circuit function. In order to do so, it is necessary to elucidate the pathophysiological processes involved in Aβ-induced neuronal network dysfunction and the molecular processes underlying such dysfunction. Over the last decades, there has been extensive research about the molecular mechanisms involved in the effects of Aβ as well as possible neuroprotective strategies against such effects. Here we are going to review some of the intracellular pathways triggered by Aβ, which involve membrane receptors such as nicotinic-R, NMDA-R, integrins, TNF-R1, RAGE, FPRL and p75NTR and their intracellular mediators such as GSK3, PKC, PI3K, Akt, FAK, MAPK family, Src family and cdk5. Several of these pathways may constitute therapeutic targets for the treatment of the Aβ-induced neuronal network dysfunction which is, at least in part, the basis for cognitive dysfunction in AD.
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Cite this article as:
Balleza-Tapia Hugo and Pena Fernando, Pharmacology of the Intracellular Pathways Activated by Amyloid Beta Protein, Mini-Reviews in Medicinal Chemistry 2009; 9 (6) . https://dx.doi.org/10.2174/138955709788452784
DOI https://dx.doi.org/10.2174/138955709788452784 |
Print ISSN 1389-5575 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-5607 |
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