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NeuroMolecular Medicine

, Volume 10, Issue 1, pp 1–9 | Cite as

Neurodegenerative Diseases: Neurotoxins as Sufficient Etiologic Agents?

  • Christopher A. Shaw
  • Günter U. Höglinger
Original Paper

Abstract

A dominant paradigm in neurological disease research is that the primary etiological factors for diseases such as Alzheimer’s (AD), Parkinson’s (PD), and amyotrophic lateral sclerosis (ALS) are genetic. Opposed to this perspective are the clear observations from epidemiology that purely genetic casual factors account for a relatively small fraction of all cases. Many who support a genetic etiology for neurological disease take the view that while the percentages may be relatively small, these numbers will rise in the future with the inevitable discoveries of additional genetic mutations. The follow up argument is that even if the last is not true, the events triggered by the aberrant genes identified so far will be shown to impact the same neuronal cell death pathways as those activated by environmental factors that trigger most sporadic disease cases. In this article we present a countervailing view that environmental neurotoxins may be the sole sufficient factor in at least three neurological disease clusters. For each, neurotoxins have been isolated and characterized that, at least in animal models, faithfully reproduce each disorder without the need for genetic co-factors. Based on these data, we will propose a set of principles that would enable any potential toxin to be evaluated as an etiological factor in a given neurodegenerative disease. Finally, we will attempt to put environmental toxins into the context of possible genetically-determined susceptibility.

Keywords

Neurological disease cluster Atypical parkinsonism Parkinsonism-dementia complex ALS Progressive subranuclear palsy Guam Guadeloupe Cycad Annonacin Sterol glucosides MPTP Environmental toxins 

Notes

Acknowledgments

This work was supported by the US Army Medical Research and Materiel Command (#DAMD17-02-1-0678), Scottish Rite Charitable Foundation of Canada, and the Natural Science and Engineering Research Council of Canada (NSERC), and NINDS to CAS and European Union Grant LSHM-CT-2003-503330 to GUH. The authors thank Michael Petrik, Dr. Reyniel Cruz-Aguado and Dr. Denis Kay for helpful suggestions and commentary.

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Copyright information

© Humana Press Inc. 2007

Authors and Affiliations

  • Christopher A. Shaw
    • 1
    • 2
    • 4
  • Günter U. Höglinger
    • 3
  1. 1.Department of OphthalmologyUniversity of British ColumbiaVancouverCanada
  2. 2.Department of Experimental Medicine and the Neuroscience ProgramUniversity of British ColumbiaVancouverCanada
  3. 3.Experimental NeurologyPhilipps UniversityMarburgGermany
  4. 4.Neural Dynamics Research GroupVancouverCanada

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