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Neurophysiological Mechanisms Underlying Cortical Hyper-Excitability in Amyotrophic Lateral Sclerosis: A Review

Amyotrophic lateral sclerosis (ALS) is a progressive neuromotor disease characterized by the loss of upper and lower motor neurons (MNs), resulting in muscle paralysis and death. Early cortical hyper-excitability is a common pathological process observed clinically and in animal disease models. Alth...

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Published in:	Brain sciences 2021-04, Vol.11 (5), p.549
Main Authors:	Pradhan, Jonu, Bellingham, Mark C
Format:	Article
Language:	English
Subjects:	Amyotrophic lateral sclerosis Animal diseases Animal models Disease electrophysiology Excitability Excitotoxicity Family medical history glutamate Glutamatergic transmission Hypotheses Interneurons Medical prognosis motor cortex Motor neurons Neurons Paralysis Pathology Patients Potassium Review synaptic transmission upper motor neuron
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description	Amyotrophic lateral sclerosis (ALS) is a progressive neuromotor disease characterized by the loss of upper and lower motor neurons (MNs), resulting in muscle paralysis and death. Early cortical hyper-excitability is a common pathological process observed clinically and in animal disease models. Although the mechanisms that underlie cortical hyper-excitability are not completely understood, the molecular and cellular mechanisms that cause enhanced neuronal intrinsic excitability and changes in excitatory and inhibitory synaptic activity are starting to emerge. Here, we review the evidence for an anterograde glutamatergic excitotoxic process, leading to cortical hyper-excitability via intrinsic cellular and synaptic mechanisms and for the role of interneurons in establishing disinhibition in clinical and experimental settings. Understanding the mechanisms that lead to these complex pathological processes will likely produce key insights towards developing novel therapeutic strategies to rescue upper MNs, thus alleviating the impact of this fatal disease.
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subjects	Amyotrophic lateral sclerosis Animal diseases Animal models Disease electrophysiology Excitability Excitotoxicity Family medical history glutamate Glutamatergic transmission Hypotheses Interneurons Medical prognosis motor cortex Motor neurons Neurons Paralysis Pathology Patients Potassium Review synaptic transmission upper motor neuron
title	Neurophysiological Mechanisms Underlying Cortical Hyper-Excitability in Amyotrophic Lateral Sclerosis: A Review
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