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Parkinson’s Disease

α-Synuclein and Parkin in Protein Aggregation and the Reversal of Unfolded Protein Stress

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Protein Misfolding and Disease

Part of the book series: Methods in Molecular Biology™ ((MIMB,volume 232))

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Abstract

Parkinson’s disease (PD) is the second most common neurodegenerative disorder. The prevalence of PD increases dramatically with age, affecting 1–2% of the population above 65 years (1,2). PD is characterized by a progressive loss of dopaminergic neurons in the substantia nigra, pars compacta in the brain stem. The classical symptoms are tremor, rigidity, and slowness of movements. The symptoms appear when about 70% of the dopaminergic neurons are lost, demonstrating that the degenerative process is active long before the patients become aware of the disease. In the degenerating neurons, proteinaceous inclusions named Lewy bodies are found in the cell body and Lewy neurites in the neuronal processes (3). The inclusions exhibit filamentous protein aggregates with α-synuclein being a prominent component (4–7). The definitive diagnosis of PD requires both the clinical symptoms and post mortem examination. No preventive or neuroprotective therapies exist for PD, of which treatment primarily relies on substitution therapy with dopamine precursors or agonists. Genetic predispositions as well as environmental factors increase the risk of PD, but the etiology of PD is largely unknown. In rare familial cases, PD is linked to mutations in single genes encoding α-synuclein and parkin proteins. These cases have shed light on mechanisms leading to the selective dopaminergic cell loss.

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Authors and Affiliations

  1. Department of Medical Biochemistry, Aarhus University, Aarhus, Denmark

    Lene Diness Jakobsen & Poul Henning Jensen

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  1. Lene Diness Jakobsen
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  2. Poul Henning Jensen
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  1. Research Unit for Molecular Medicine, Skejby Sygehus, Aarhus, Denmark

    Peter Bross  & Niels Gregersen  & 

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© 2003 Humana Press Inc., Totowa, NJ

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Jakobsen, L.D., Jensen, P.H. (2003). Parkinson’s Disease. In: Bross, P., Gregersen, N. (eds) Protein Misfolding and Disease. Methods in Molecular Biology™, vol 232. Humana Press. https://doi.org/10.1385/1-59259-394-1:57

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  • DOI: https://doi.org/10.1385/1-59259-394-1:57

  • Publisher Name: Humana Press

  • Print ISBN: 978-1-58829-065-6

  • Online ISBN: 978-1-59259-394-1

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