A new protective protein against Parkinson's disease

In a recent finding that broadens our understanding of axon loss in neurodegenerative disorders, researchers at the Swiss Federal Institute of Technology in Lausanne (EPFL) have shown that a spontaneous dominant mutation has a protective effect on axons in an mouse model of Parkinson's disease. Parkinson's disease is characterized by the progressive degeneration of dopaminergic neurons projecting to a well-defined structure in the brain named the striatum. The resulting failure of the nigrostriatal pathway leads to profound dopamine deficiency, causing bradykinesia, tremor and rigidity. Since the deficit in striatal dopamine is the main cause of PD symptoms, it appears critical to preserve axon terminals to ensure healthy functioning of the nigrostriatal system.

Previous work had shown that a spontaneous dominant mutation in the mouse, Wlds (slow Wallerian degeneration), is associated with the protection of axons from a process known as peripheral nerve Wallerian degeneration -- that is, degeneration of axons following a physical insult that disconnects the axons from neuronal cell bodies. The Wlds mutation results in the formation of an abnormal fusion protein whose molecular effects aren't well understood, but the axonal protection conferred by the mutation suggests therapeutic potential for manipulating the biological pathways involved.

In the present work, these scientists sought to assess the effects of the Wlds protein in mouse model of Parkinson's disease. The researchers found that following injection of a dopamine toxin in the brain (a technique that mimics Parkinson's Disease), Wlds mutant mice exhibited strong protection of dopaminergic axons. Moreover, the ability of the preserved axons to synthesize and release dopamine was confirmed by behavioural data. Interestingly, while axons were protected, there was no accompanying protection of the dopaminergic cell bodies in Wlds mice, highlighting subtle differences in the degeneration process between neuronal sub-cellular compartments. This newly reported Wlds-mediated protection of the dopamine axons may lead to the understanding of mechanisms underlying axon loss and to the development of new therapeutic approaches for Parkinson disease.

Ali Sajadi, Bernard L. Schneider, and Patrick Aebischer: "Wlds-Mediated Protection of Dopaminergic Fibers in an Animal Model of Parkinson Disease"

Published in Current Biology, Volume 14, Number 4 February 17, 2004, pages 326-330.

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