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The Interplay Between Proteostasis Systems and Parkinson's Disease

Lookup NU author(s): Professor Tiago OuteiroORCiD


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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.

Publication metadata

Author(s): Lazaro DF, Outeiro TF

Publication type: Book Chapter

Publication status: Published

Book Title: Advances in experimental medicine and biology

Year: 2020

Volume: 1233

Pages: 223-236

Online publication date: 10/04/2020

Acceptance date: 02/04/2016

Series Title: Advances in Experimental Medicine and Biology (AEMB)

Publisher: Springer


DOI: 10.1007/978-3-030-38266-7_9

PubMed id: 32274759

Library holdings: Search Newcastle University Library for this item

ISBN: 9783030382667