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Is Trophic Factor Gene Disruption a “Knockout” Model for Parkinson’s Disease?

  • Chapter
Central Nervous System Diseases

Part of the book series: Contemporary Neuroscience ((CNEURO))

Abstract

Parkinson’s disease is a debilitating and progressive disease of the extrapyramidal motor system that occurs due to the degeneration of dopaminergic (DAergic) neurons in the ventral mesencephalic (VM) nucleus substantia nigra (1). Despite numerous hypotheses and continued speculation, the triggering mechanisms for this degeneration of the DA neurons remain unknown. Recent studies have suggested that mitochondrial oxidative dysfunction may cause premature cell death and may be linked to accelerated apoptosis, excessive free and toxic radicals, deficient neurotrophic factors, or some combination thereof (2–6). It has, for example, been shown that certain substances can give rise to significant apoptotic changes in these neurons, such as levodopa (7), DA-melanin (8), 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP; 9), hypoischemia (10), as well as axonal transection (11,12). The standard therapeutic intervention to date is the administration of the DA precursor levo-Dopa, or L-Dopa (13,14). However, with the progression of the disease this drug is less effective, and continued administration also leads to significant negative side effects such as hallucinations and hyperkinesia (1,13). Therefore, much research effort has been put forth during recent years to develop alternative treatment strategies.

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Authors
  1. Ann-Charlotte Granholm
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  2. Barry Hoffer
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Editors and Affiliations

  1. Alkermes, Inc., Cambridge, MA, USA

    Dwaine F. Emerich PhD (Director of Neuroscience) (Director of Neuroscience)

  2. Department of Neuroscience, Alkermes, Inc., Cambridge, MA, USA

    Reginald L. Dean III MS

  3. University of South Florida College of Medicine, Tampa, FL, USA

    Paul R. Sanberg PhD, DSc

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Granholm, AC., Hoffer, B. (2000). Is Trophic Factor Gene Disruption a “Knockout” Model for Parkinson’s Disease?. In: Emerich, D.F., Dean, R.L., Sanberg, P.R. (eds) Central Nervous System Diseases. Contemporary Neuroscience. Humana Press, Totowa, NJ. https://doi.org/10.1007/978-1-59259-691-1_13

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  • DOI: https://doi.org/10.1007/978-1-59259-691-1_13

  • Publisher Name: Humana Press, Totowa, NJ

  • Print ISBN: 978-1-61737-152-3

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