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Excitotoxicity in ALS: Overstimulation, or overreaction?

Citation

King, AE and Woodhouse, A and Kirkcaldie, MTK and Vickers, JC, Excitotoxicity in ALS: Overstimulation, or overreaction?, Experimental Neurology, 275 pp. 162-171. ISSN 0014-4886 (2016) [Refereed Article]

Copyright Statement

2015 Elsevier Inc. All rights reserved.

DOI: doi:10.1016/j.expneurol.2015.09.019

Abstract

Amyotrophic lateral sclerosis (ALS) is an adult onset neurodegenerative disease that results in motor dysfunction and death, generally from respiratory failure. 90% of ALS cases are sporadic with no known cause. Familial cases have been linked with mutations in several disparate classes of genes, including those involved in DNA/RNA metabolism, protein misfolding, oxidative stress and the cytoskeleton, leading to the proposition that ALS could be a multi-factorial disease. However, alterations in excitability have been reported in all types of ALS cases, and may be a common disease mechanism predisposing neurons to degeneration. Excitotoxicity has long been suspected as a mediator in the disease process, and may arise from changes in synaptic inputs, or alterations in the excitability of the neurons being stimulated. Although the glutamatergic system is widely recognised as a therapeutic avenue with the potential to extend lifespan and delay disease onset, the causes of altered excitability in ALS are currently unclear and warrant further investigation. This article reviews current evidence of alterations to excitatory and inhibitory signalling in the cortex and spinal cord, and in the intrinsic excitability of motor neurons, in ALS.

Item Details

Item Type:Refereed Article
Keywords:excitotoxicity, ALS, motor neuron disease, glutamate, GABA, glycine, interneuron EAAT2, neuronal excitability
Research Division:Medical and Health Sciences
Research Group:Neurosciences
Research Field:Cellular Nervous System
Objective Division:Health
Objective Group:Clinical Health (Organs, Diseases and Abnormal Conditions)
Objective Field:Nervous System and Disorders
Author:King, AE (Associate Professor Anna King)
Author:Woodhouse, A (Dr Adele Woodhouse)
Author:Kirkcaldie, MTK (Dr Matthew Kirkcaldie)
Author:Vickers, JC (Professor James Vickers)
ID Code:104915
Year Published:2016 (online first 2015)
Web of Science® Times Cited:37
Deposited By:Medicine (Discipline)
Deposited On:2015-11-25
Last Modified:2017-11-06
Downloads:0

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