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Cellular and Molecular Mechanisms Underlying Parkinson’s Disease: The Role of Molecular Chaperones

  • Pamela J. Mclean
Part of the Heat Shock Proteins book series (HESP, volume 3)

Abstract

Adult onset neurodegenerative diseases are thought to be caused by toxic misfolded proteins. Triggered by gene mutations and environmental events, toxic proteins cause cell death in various brain regions and accumulate in intraneuronal inclusion bodies. In Parkinson’s disease (PD), Lewy bodies (LBs) containing the small acidic protein, α-synuclein, are found at autopsy making α-synuclein a candidate for the toxic protein in PD and other synucleinopathies such as dementia with Lewy bodies (DLB), where the pathology extends into the cortex. Normally, mutant proteins that fail to fold properly are either refolded by molecular chaperones or degraded by the proteasome or lysosome. The ineffectiveness of these quality control mechanisms in neurodegenerative diseases such as Parkinson’s disease may be due, at least in part, to a natural decline in function of the aging brain. The result is the accumulation of misfolded protein and a disruption in cellular function. Here, we will examine the emerging role of heat shock protein molecular chaperones in Parkinson’s disease and investigate the potential targeting of heat shock protein molecular chaperones as therapeutic drug targets

α-synuclein Parkinson’s disease dementia with Lewy bodies heat shock proteins protein misfolding neurodegeneration 

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© Springer Science+Business Media B.V. 2008

Authors and Affiliations

  • Pamela J. Mclean
    • 1
  1. 1.Mass General Institute for Neurodegenerative Disease (MIND)Massachusetts General HospitalCharlestownUSA

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