Researchers untangle molecular pathology of giant axonal neuropathy

Giant axonal neuropathy (GAN) is a rare genetic disorder that causes central and peripheral nervous system dysfunction. GAN is known to be caused by mutations in the gigaxonin gene and is characterized by tangling and aggregation of neural projections, but the mechanistic link between the genetic mutation and the effects on neurons is unclear.

In this issue of the Journal of Clinical Investigation, Robert Goldman and colleagues at Northwestern University uncover how mutations in gigaxonin contribute to neural aggregation.They demonstrated that gigaxonin regulates the degradation of neurofilament proteins, which help to guide outgrowth and morphology of neural projections.

Loss of gigaxonin in either GAN patient cells or increased levels of neurofilament proteins, causing tangling and aggregation of neural projections. Importantly, expression of gigaxonin allowed for clearance of neurofilament proteins in neurons.

These findings demonstrate that mutations in gigaxonin cause accumulation of neurofilament proteins and shed light on the molecular pathology of GAN.

More information: Giant axonal neuropathy–associated gigaxonin mutations impair intermediate filament protein degradation, J Clin Invest. doi:10.1172/JCI66387

add to favorites email to friend print save as pdf

Related Stories

A gut feeling about neural stem cells

Feb 01, 2013

Proper function of the digestive system requires coordinated contraction of the muscle in the wall of the intestinal tract, regulated by the enteric nervous system. Damage or loss of these neurons can result in intestinal ...

Recommended for you

Brainwaves can predict audience reaction

4 hours ago

Media and marketing experts have long sought a reliable method of forecasting responses from the general population to future products and messages. According to a study conducted at The City College of New ...

Continuing the quest for better stroke therapies

Jul 29, 2014

Helping people recover from the debilitating effects of a stroke is an immensely complex challenge that requires deep knowledge of neurophysiology as well as effective therapy. Advancing such knowledge to improve therapeutic ...

User comments