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Neurodegener Dis Manag. 2015 Dec;5(6):511-25. doi: 10.2217/nmt.15.49. Epub 2015 Nov 30.

Inhibitory dysfunction in amyotrophic lateral sclerosis: future therapeutic opportunities.

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Menzies Institute for Medical Research, University of Tasmania, Hobart TASĀ 7000, Australia.


In amyotrophic lateral sclerosis, motor neuron hyperexcitability and inhibitory dysfunction is emerging as a potential causative link in the dysfunction and degeneration of the motoneuronal circuitry that characterizes the disease. Interneurons, as key regulators of excitability, may mediate much of this imbalance, yet we know little about the way in which inhibitory deficits perturb excitability. In this review, we explore inhibitory control of excitability and the potential contribution of altered inhibition to amyotrophic lateral sclerosis disease processes and vulnerabilities, identifying important windows of therapeutic opportunity and potential interventions, specifically targeting inhibitory control at key disease stages.


amyotrophic lateral sclerosis; excitability; hyperexcitability; hypoexcitability; inhibition; interneuron; motor neuron

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