Abstract
It is well accepted that cortical and hippocampal synaptic densities are reduced in Alzheimer’s disease (AD). These alterations in neuronal networking occur at the very onset of AD and may lead to the neuronal loss displayed in later stages of the disease, which is characterized by severe cognitive and behavioral impairments. Many studies suggest that amyloid-β (Aβ) oligomers are responsible for synaptic disconnections and neuronal death. The effects of Aβ in different brain regions are pleotropic, thus suggesting a common mechanism for toxicity. One potential site for this mechanism of toxicity is the neuronal membrane. It is recognized that Aβ can associate to the plasma membrane and induce the formation of pores after the interaction with lipids like GM1 and cholesterol, and proteins such as APP and NMDA receptors. After this early event, the membrane increases its permeability allowing the influx of small ions and larger molecules. Thus, one of the main toxic consequences of Aβ oligomer interaction with neurons is an increase in intracellular Ca2+ concentration that causes alterations in ionic homeostasis. It has been proposed that Aβ perforates the membrane similarly to pore-forming toxins producing a series of effects that include synaptic failure and cell death. These actions of Aβ appear to be potentiated by neuroinflammation, which results in a series of effects that, when prolonged, will affect membrane integrity, pore formation and cellular homeostasis. Here, we will review the most recent data on Aβ actions at the membrane level and how its relationship with neuroinflammation could further potentiate brain impairment in AD. The notion of having drugs acting with dual inhibitory actions, inhibition of membrane damage and inflammation, could serve as a starting conceptual point for the development of new therapies for the disease.
Keywords: Amyloid beta, neuroinflammation, amyloid pore, membrane, Alzheimer, lipid, protein.
Current Pharmaceutical Design
Title:Membrane Damage Induced by Amyloid Beta and a Potential Link with Neuroinflammation
Volume: 22 Issue: 10
Author(s): Eduardo J. Fernandez-Perez, Christian Peters and Luis G. Aguayo
Affiliation:
Keywords: Amyloid beta, neuroinflammation, amyloid pore, membrane, Alzheimer, lipid, protein.
Abstract: It is well accepted that cortical and hippocampal synaptic densities are reduced in Alzheimer’s disease (AD). These alterations in neuronal networking occur at the very onset of AD and may lead to the neuronal loss displayed in later stages of the disease, which is characterized by severe cognitive and behavioral impairments. Many studies suggest that amyloid-β (Aβ) oligomers are responsible for synaptic disconnections and neuronal death. The effects of Aβ in different brain regions are pleotropic, thus suggesting a common mechanism for toxicity. One potential site for this mechanism of toxicity is the neuronal membrane. It is recognized that Aβ can associate to the plasma membrane and induce the formation of pores after the interaction with lipids like GM1 and cholesterol, and proteins such as APP and NMDA receptors. After this early event, the membrane increases its permeability allowing the influx of small ions and larger molecules. Thus, one of the main toxic consequences of Aβ oligomer interaction with neurons is an increase in intracellular Ca2+ concentration that causes alterations in ionic homeostasis. It has been proposed that Aβ perforates the membrane similarly to pore-forming toxins producing a series of effects that include synaptic failure and cell death. These actions of Aβ appear to be potentiated by neuroinflammation, which results in a series of effects that, when prolonged, will affect membrane integrity, pore formation and cellular homeostasis. Here, we will review the most recent data on Aβ actions at the membrane level and how its relationship with neuroinflammation could further potentiate brain impairment in AD. The notion of having drugs acting with dual inhibitory actions, inhibition of membrane damage and inflammation, could serve as a starting conceptual point for the development of new therapies for the disease.
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Cite this article as:
Fernandez-Perez J. Eduardo, Peters Christian and Aguayo G. Luis, Membrane Damage Induced by Amyloid Beta and a Potential Link with Neuroinflammation, Current Pharmaceutical Design 2016; 22 (10) . https://dx.doi.org/10.2174/138161282210160304111702
DOI https://dx.doi.org/10.2174/138161282210160304111702 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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