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The Proteasome, Protein Aggregation, and Neurodegeneration

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Handbook of Neurochemistry and Molecular Neurobiology

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Abstract:

The presence of intracellular inclusions containing aggregated proteins feature in affected neurons of patients with neurodegenerative disease. Such inclusions also contain immunoreactive ubiquitin and proteasome subunits. Similar perinuclear inclusions termed aggresomes are formed when cells are treated with proteasome inhibitors. Since unfolded proteins are predominantly degraded by the ubiquitin-proteasome system (UPS), a dysfunction of this system has been proposed to contribute to neurodegeneration. This chapter presents an outline of the biochemistry of the UPS followed by an examination of the experimental evidence relating this protein-degrading system to Parkinson's disease, to protein aggregation and aggresome formation, and to polyglutamine disease.

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Abbreviations

ARJP:

autosomal recessive juvenile Parkinsonism

AZ:

antizyme

CFTR:

Cystic fibrosis transmembrane conductance regulator

CHIP:

carboxyl terminus of Hsc-70-interacting protein

INF-γ:

Interferon gamma

NII:

neuronal intranuclear inclusions

ODC:

ornithine decarboxylase

Pael-R:

Parkin-associated endothelin receptor-like receptor

PGPH:

peptidyl glutamyl peptide hydrolyzing

PSI:

Z-lle-Glu(O-tBu)-Ala-leucinal

UIM:

ubiquitin-interacting motif

UPS:

ubiquitin-proteasome system

Z:

N-benzyloxycarbonyl

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Editors and Affiliations

  1. Center for Neurochemistry, Nathan S. Kline Institute for Psychiatric Research, 140 Old Orangeburg Road, Orangeburg, Newyork, 10962, USA

    Abel Lajtha (Director) (Director)

  2. Department of Neurosciences Division of Neurology, Medical University of South Carolina, 96 Jonathan Lucas Street Suite 309, Charleston, SC 29425, USA

    Naren Banik (Professor) (Professor)

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Wilk, S. (2007). The Proteasome, Protein Aggregation, and Neurodegeneration. In: Lajtha, A., Banik, N. (eds) Handbook of Neurochemistry and Molecular Neurobiology. Springer, Boston, MA. https://doi.org/10.1007/978-0-387-30379-6_13

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