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Oxidative protein damage and the proteasome

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Abstract

Protein damage, caused by radicals, is involved in many diseases and in the aging process. Therefore, it is crucial to understand how protein damage can be limited, repaired or removed. To degrade damaged proteins, several intracellular proteolytic systems exist. One of the most important contributors in intracellular protein degradation of oxidized, aggregated and misfolded proteins is the proteasomal system. The proteasome is not a simple, unregulated structure. It is a more complex proteolytic composition that undergoes diverse regulation in situations of oxidative stress, aging and pathology. In addition to that, numerous studies revealed that the proteasome activity is altered during life time, contributing to the aging process. In addition, in the nervous system, the proteasome plays an important role in maintaining neuronal protein homeostasis. However, alterations in the activity may have an impact on the onset of neurodegenerative diseases. In this review, we discuss what is presently known about protein damage, the role of the proteasome in the degradation of damaged proteins and how the proteasome is regulated. Special emphasis was laid on the role of the proteasome in neurodegenerative diseases.

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Abbreviations

AD:

Alzheimer's disease

ATP:

Adenosine triphosphate

γ-IFN:

Interferon-gamma

HD:

Huntington's disease

HSP:

Heat shock protein

MHC-I:

Major histocompatibility complex class I

PARP:

Poly-(ADP-ribose) polymerase

PHF:

Tau-based paired helical filaments

PD:

Parkinson's disease

ROS:

Reactive oxygen species

UCH-L1:

Ubiquitin carboxyl terminal hydrolase L1

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  1. Department of Biofunctionality and Food Safety, Institute of Biological Chemistry and Nutrition, University of Hohenheim, Garbenstr. 28, 70593, Stuttgart, Germany

    S. Grimm, A. Höhn & T. Grune

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  1. S. Grimm
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  2. A. Höhn
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Grimm, S., Höhn, A. & Grune, T. Oxidative protein damage and the proteasome. Amino Acids 42, 23–38 (2012). https://doi.org/10.1007/s00726-010-0646-8

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