Impairments of inhibitory neurons in amyotrophic lateral sclerosis and frontotemporal dementia.

Neurobiology of Disease 2024 5 cites
2024:12025:22026:2
2024 2026
5

["Lorenc F\u00e9licie", "Dupuis Luc", "Cassel Raphaelle"]

Abstract

Amyotrophic lateral sclerosis and frontotemporal dementia are two fatal neurodegenerative disorders. They are part of a pathophysiological continuum, displaying clinical, neuropathological, and genetic overlaps. There is compelling evidence that neuronal circuit dysfunction is an early feature of both diseases. Impaired neuronal excitability, imbalanced excitatory and inhibitory influences, and altered functional connectivity have been reported. These phenomena are likely due to combined alterations in the various cellular components involved in the functioning of neuronal networks. This review focuses on one of these cellular components: inhibitory neurons. We assess the evidence for inhibitory neuron impairments in amyotrophic lateral sclerosis and frontotemporal dementia, as well as the mechanisms leading to the loss of inhibition. We also discuss the contributions of these alterations to symptoms, and the potential therapeutic strategies for targeting inhibitory neuron deficits.

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