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Scientific News: Schwann Cells and Mitochondrial Deficits

5/22/2013
 
Aberrant Schwann Cell Lipid Metabolism Linked to Mitochondrial Deficits Leads to Axon Degeneration and Neuropathy
 
Mitochondrial dysfunction in mice may lead to peripheral neuropathies such as diabetes, according to a recent article in Neuron 77 *. Also, it may contribute to adult-onset neurodegenerative disorders including ALS and Parkinson’s Disease. In this study, Viader and colleagues investigated a mouse model of peripheral neuropathy secondary to Schwann cells (SC) mitochondrial dysfunction (Tfam-SCKos).
 
In the mouse model, Tfam controls the transcription, replication, and stability of mitochondrial DNA. Its depletion causes a failure of key components of the electron transport chain, which leads to respiratory deficiency and abnormal mitochondrial morphology in SC. Disruption of this mitochondria structure activates a maladaptive stress response through the actions of Heme regulated kinase. In turn, this causes a shift in lipid metabolism that favors oxidation rather than fatty acid synthesis. These alterations lead to depletion of important myelin lipid components (cerebrosides/sulfatides--constitute about 30% of peripheral myelin), which: 
 
  • Leads to problems in saltatory conduction of action potentials,
  • Interferes with maintenance of SC-axon contacts, and 
  • Ion channel clustering around the nodes of Ranvier.  
 
In addition, a buildup of acylcarnitines, an intermediate of fatty acid beta oxidation, is released from SC, inducing axonal degeneration. Thus, both processes of demyelination and axonal loss are thought to occur during this process. 
 
Comments: Mitochondrial dysfunction has long been recognized as a key contributor to certain forms of peripheral neuropathy. However, previous studies have examined the role of neuronal mitochondria in the pathogenesis of peripheral neuropathy. The authors propose that disruption of SC mitochondria alters lipid metabolism, especially that of oxidation, resulting in the accumulation of acylcarnitines and depletion of critical myelin lipids. In turn, it may allow for new therapeutic strategies that prevent depletion of lipids that supports axo-glial interactions and block accumulation of fatty acid intermediates that lead to axonal toxicity. In addition, better treatment in patients with mitochondrial-related peripheral nerve disorders and diabetic neuropathy may be possible.
 
* Viader, Et Al, Neuron 77, March 6, 2013, pages 886-898

This review was submitted by the News Science Editorial Board.


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