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Updated: Aug 23, 2026

Assays for the Degradation of Misfolded Proteins in Cells
Published on: August 28, 2016
Accumulation of aberrant ubiquitin induces aggregate formation and cell death in polyglutamine diseases
Remko de Pril1, David F Fischer, Marion L C Maat-Schieman
1Research Team Molecular Misreading, Netherlands Institute for Brain Research, Amsterdam, The Netherlands.
Abstract:
Polyglutamine diseases are characterized by neuronal intranuclear inclusions (NIIs) of expanded polyglutamine proteins, indicating the failure of protein degradation. UBB(+1), an aberrant form of ubiquitin, is a substrate and inhibitor of the proteasome, and was previously reported to accumulate in Alzheimer disease and other tauopathies. Here, we show accumulation of UBB(+1) in the NIIs and the cytoplasm of neurons in Huntington disease and spinocerebellar ataxia type-3, indicating inhibition of the proteasome by polyglutamine proteins in human brain. We found that UBB(+1) not only increased aggregate formation of expanded polyglutamines in neuronally differentiated cell lines, but also had a synergistic effect on apoptotic cell death due to expanded polyglutamine proteins. These findings implicate UBB(+1) as an aggravating factor in polyglutamine-induced neurodegeneration, and clearly identify an important role for the ubiquitin-proteasome system in polyglutamine diseases.
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