The Proteasome Inhibition Model of Parkinson's disease

Onderzoeksoutput: Article

46 Citaten (Scopus)

Samenvatting

The pathological hallmarks of Parkinson's disease are the progressive loss of nigral dopaminergic neurons and the formation of intracellular inclusion bodies, termed Lewy bodies, in surviving neurons. Accumulation of proteins in large insoluble cytoplasmic aggregates has been proposed to result, partly, from a failure in the function of intracellular protein degradation pathways. Evidence in support for such a hypothesis emerged in the beginning of the years 2000 with studies demonstrating structural and functional deficits in the ubiquitin-proteasome pathway in post-mortem nigral tissue of patients with Parkinson's disease. These fundamental findings have inspired the development of a new generation of animal models based on the use of proteasome inhibitors to disturb protein homeostasis and trigger nigral dopaminergic neurodegeneration. In this review, we provide an updated overview of the current approaches in employing proteasome inhibitors to model Parkinson's disease, with particular emphasis on rodent studies. In addition, the mechanisms underlying proteasome inhibition-induced cell death and the validity criteria (construct, face and predictive validity) of the model will be critically discussed. Due to its distinct, but highly relevant mechanism of inducing neuronal death, the proteasome inhibition model represents a useful addition to the repertoire of toxin-based models of Parkinson's disease that might provide novel clues to unravel the complex pathogenesis of this disorder.

Originele taal-2English
Pagina's (van-tot)31-63
Aantal pagina's33
TijdschriftJournal of Parkinson's Disease
Volume7
Nummer van het tijdschrift1
DOI's
StatusPublished - 2017

Vingerafdruk

Duik in de onderzoeksthema's van 'The Proteasome Inhibition Model of Parkinson's disease'. Samen vormen ze een unieke vingerafdruk.

Citeer dit