The Wld(S) mutation delays anterograde, but not retrograde, axonal degeneration of the dopaminergic nigro-striatal pathway in vivo.

Journal of Neurochemistry
Hsiao-Chun Cheng, Robert E Burke

Abstract

For many neurodegenerative disorders, such as Parkinson's disease, there is evidence that the disease first affects axons and terminals of neurons that are selectively vulnerable. This would suggest that it may be possible to forestall progression by targeting the cellular mechanisms of axon degeneration. While it is now clear that these mechanisms are distinct from the pathways of programmed cell death, they are less well known. Compelling evidence of the distinctiveness of these mechanisms has derived from studies of the Wld(S) mutation, which confers resistance to axon degeneration. Little is known about how this mutation affects degeneration in dopaminergic axons, those that are affected in Parkinson's disease. We have characterized the Wld(S) phenotype in these axons in four models of injury: two that utilize the neurotoxin 6-hydroxydopamine or axotomy to induce anterograde degeneration, and two that use these methods to induce retrograde degeneration. For both 6-hydroxydopamine and axotomy, Wld(S) provides protection from anterograde, but not retrograde degeneration. This protection is observed as preserved immunostaining for tyrosine hydroxylase in axons and striatum, and by structural integrity visualized by GFP in tyro...Continue Reading

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Citations

Mar 7, 2012·Cell and Tissue Research·Paul LingorMathias Bähr
Jan 31, 2012·Experimental Neurology·Robert E Burke, Karen O'Malley
May 21, 2014·Nature Reviews. Neuroscience·Laura ConfortiMichael P Coleman
Jun 3, 2014·Molecular Neurodegeneration·Xi LuKaren L O'Malley
Mar 15, 2014·Disease Models & Mechanisms·Kelley C O'DonnellAlvaro Sagasti
Mar 26, 2011·Annals of Neurology·Sang Ryong KimRobert E Burke
Mar 24, 2016·Journal of Parkinson's Disease·Patricia Tagliaferro, Robert E Burke
Dec 25, 2012·Experimental Neurology·Suraj Pradhan, Katrin Andreasson
Jan 18, 2019·Movement Disorders : Official Journal of the Movement Disorder Society·Stanley FahnSusan Bressman
Oct 22, 2019·Current Opinion in Neurology·Vassilis E Koliatsos, Athanasios S Alexandris
Nov 26, 2019·Cell Chemical Biology·Heather S Loring, Paul R Thompson
Apr 24, 2021·Neurobiology of Disease·Owen M PetersMarc Freeman

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