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The Interplay Between Proteostasis Systems and Parkinson’s Disease

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Proteostasis and Disease

Part of the book series: Advances in Experimental Medicine and Biology ((AEMB,volume 1233))

Abstract

The proteostasis network controls the balance between protein synthesis, folding, function, and degradation, and ensures proteins are recycled when they are no longer needed or become damaged, avoiding unwanted aggregation and accumulation. In various neurological disorders, such as Parkinson’s disease (PD) and other synucleinopathies, the accumulation of misfolded and aggregated alpha-synuclein (aSyn) is considered a central event in the onset and progression of disease. During aging, there is a decline in the activity of various degradation machineries, and the overall buffering capacity of the proteostasis network starts to decrease. Such decline is thought to play a pivotal role in PD, causing aSyn to build-up due to compromised clearance, which in turn contributes to further disease progression.

In this chapter, we summarize central findings related to aSyn accumulation and degradation, as well as to the consequences of the toxic effects caused by aSyn on proteostasis. We also highlight some of the factors and pathways that may be used as potential targets for therapeutic interventions in PD.

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Acknowledgments

TFO is supported by an EU Joint Programme—Neurodegenerative Disease Research (JPND) project (aSynProtec) and by the European Union’s Horizon 2020 research and innovation programme under grant agreement No. 721802. TFO and DFL are supported by a grant from ParkinsonFonds Deutschland (PD).

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Authors and Affiliations

  1. Department of Experimental Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany

    Diana F. Lázaro & Tiago F. Outeiro

  2. Center for Biostructural Imaging of Neurodegeneration, University Medical Center Göttingen, Göttingen, Germany

    Diana F. Lázaro & Tiago F. Outeiro

  3. Max Planck Institute for Experimental Medicine, Göttingen, Germany

    Tiago F. Outeiro

  4. Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne, UK

    Tiago F. Outeiro

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  1. Diana F. Lázaro
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  2. Tiago F. Outeiro
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Correspondence to Tiago F. Outeiro .

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  1. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    Rosa Barrio

  2. CIC bioGUNE, Basque Research and Technology Alliance (BRTA), Derio, Spain

    James D. Sutherland

  3. Centre Pierre Potier, ITAV, Toulouse Cedex 1, France

    Manuel S. Rodriguez

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Lázaro, D.F., Outeiro, T.F. (2020). The Interplay Between Proteostasis Systems and Parkinson’s Disease. In: Barrio, R., Sutherland, J., Rodriguez, M. (eds) Proteostasis and Disease . Advances in Experimental Medicine and Biology, vol 1233. Springer, Cham. https://doi.org/10.1007/978-3-030-38266-7_9

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