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Giant axonal neuropathy: studies with sulfhydryl donor compounds
R Tandan1, W G Bradley, M J Fillyaw
1Department of Neurology, University of Vermont College of Medicine, Burlington.
Journal of the Neurological Sciences
|February 1, 1990
Summary
Giant axonal neuropathy (GAN) involves abnormal neurofilament and vimentin accumulation. Treatment with sulfhydryl donors like penicillamine showed clinical improvement, suggesting disordered thiol metabolism in GAN.
Area of Science:
- Neuroscience
- Cell Biology
- Biochemistry
Background:
- Giant axonal neuropathy (GAN) is a rare genetic disorder affecting peripheral nerves.
- Pathologically, GAN is characterized by neurofilament accumulation within axons and vimentin in fibroblasts.
- Acrylamide and toxic hexacarbons induce similar neurofibrillary disorders by binding to thiol groups.
Observation:
- GAN fibroblasts exhibit vimentin filament aggregation.
- Dithiothreitol and penicillamine, sulfhydryl donor compounds, were used to treat GAN fibroblasts.
- These compounds are known to stabilize thiols.
Findings:
- Dithiothreitol and penicillamine inhibited vimentin filament aggregation in GAN fibroblasts.
- A patient with GAN showed clinical improvement after treatment with penicillamine.
- This improvement occurred despite the patient's previously progressive disease course.
Implications:
- The findings support a hypothesis of disordered thiol metabolism in GAN.
- This research opens new avenues for understanding and potentially treating GAN.
- Targeting thiol metabolism may offer a therapeutic strategy for GAN patients.