August 12, 2016

New culprit in nerve degeneration

Vanderbilt researchers have discovered that regulation of cell volume plays a role in nerve degeneration and peripheral neuropathies.

Proteins that move potassium and chloride ions across the cell membrane – KCC proteins – play important roles in cell volume regulation, epithelial transport and neuronal excitability. A team of investigators has now implicated KCC3 in a peripheral neuropathy primarily affecting motor neurons.

Eric Delpire, Ph.D., and colleagues identified a mutation in the gene encoding KCC3 in a patient with an early-onset, progressive and severe peripheral motor neuropathy.

They demonstrated in patient cells that the mutation caused KCC3 to be constantly active – not turned on and off in response to cellular conditions – and that this constant activity compromised the regulation of cell volume. Mice expressing the mutant KCC3 developed similar clinical, electrophysiological and histological aspects of the disease in the patient.

The findings, reported in the Aug. 2 issue of Science Signaling, implicate abnormal cell volume control as a previously unreported mechanism of axonal degeneration and identify KCC3 as a potential therapeutic target for peripheral neuropathies.

This research was supported by the National Institutes of Health (grant GM074771).

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