About this Research Topic
Dementias are known to be a worldwide epidemiological problem. The importance of understanding the molecular basis of dementias and designing rational therapies for its treatment is of growing interest for populations where life expectancy together with concerns for a better quality of life are increasing. Together with Parkinson's disease, Huntington's disease, transmissible spongiform encephalopathies and amyotrophic lateral sclerosis, Alzheimer disease (AD) is one of the diverse neurodegenerative diseases that present a pathological common mechanism consistent on conformational disorders of a particular protein which can fold into a stable alternative conformation. In most cases, this alteration results in its aggregation and accumulation in tissues as fibrillar deposits that finally induce neuronal death. However, at early stages, the mechanistic link between progressive cognitive impairment associated with neurodegenerative disorder has not been elucidated yet.
Based on these findings, and tempting to find an explanation for cognitive deficits observed in preclinical AD patients when no significant decline in the synapse and cell number has been detected, it has been proposed that misfolded oligomeric forms or small Aβ aggregates that are not deposited in the tissue might induce an initial state of synaptic dysfunction. The chronicity of this state will lead the brain to employ compensatory tools that over time will fail by loss of tuning between excitatory and inhibitory activities.
During the last decade it has been suggested the emerging concept that the synaptic dysfunction caused by Aβ underlying the imbalance between excitatory and inhibitory neurotransmission systems, also explain hippocampal and cortical oscillatory impairments and hyperactivity found in early stage of AD. Recently it has been shown that Aβ modulates the activity of different receptors/channels which directly control the neuronal excitability, such as sodium or potassium channels. Pharmacological treatments based on the reestablishment of neuronal excitability level have shown to improve AD symptoms, so that strategies aimed to restore the balance between excitatory and inhibitory systems, particularly in early stages of the disease, seem to be the most appropriated to act on the functional deficits caused by Aβ.
Our main focus in this Research Topic will be on the most recent developments and ideas in the field of control of the neuronal excitability and oscillatory activity, which will enable us to discuss therapeutic opportunities for the near future. Accordingly, this Topic is particularly, but not exclusively, interested in the following questions:
What the Aβ molecular targets are?
How does Aβ affect synaptic function?
What are the mechanisms of Aβ-induced neural excitability changes and how can affect network activity?
What is the impact of Aβ on cellular/molecular properties of neurons, circuit functions and behavior?
Which drugs could modulate the synaptic neurotransmission dysfunction that Aβ initiates?
Based on these findings, and tempting to find an explanation for cognitive deficits observed in preclinical AD patients when no significant decline in the synapse and cell number has been detected, it has been proposed that misfolded oligomeric forms or small Aβ aggregates that are not deposited in the tissue might induce an initial state of synaptic dysfunction. The chronicity of this state will lead the brain to employ compensatory tools that over time will fail by loss of tuning between excitatory and inhibitory activities.
During the last decade it has been suggested the emerging concept that the synaptic dysfunction caused by Aβ underlying the imbalance between excitatory and inhibitory neurotransmission systems, also explain hippocampal and cortical oscillatory impairments and hyperactivity found in early stage of AD. Recently it has been shown that Aβ modulates the activity of different receptors/channels which directly control the neuronal excitability, such as sodium or potassium channels. Pharmacological treatments based on the reestablishment of neuronal excitability level have shown to improve AD symptoms, so that strategies aimed to restore the balance between excitatory and inhibitory systems, particularly in early stages of the disease, seem to be the most appropriated to act on the functional deficits caused by Aβ.
Our main focus in this Research Topic will be on the most recent developments and ideas in the field of control of the neuronal excitability and oscillatory activity, which will enable us to discuss therapeutic opportunities for the near future. Accordingly, this Topic is particularly, but not exclusively, interested in the following questions:
What the Aβ molecular targets are?
How does Aβ affect synaptic function?
What are the mechanisms of Aβ-induced neural excitability changes and how can affect network activity?
What is the impact of Aβ on cellular/molecular properties of neurons, circuit functions and behavior?
Which drugs could modulate the synaptic neurotransmission dysfunction that Aβ initiates?
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