Journal Article

Ubiquilin 2 Is Not Associated with Tau Pathology

van Haastert, Elise S., Hoozemans, Jeroen J. M., Nölle, Anna, Zwart, Rob, Scheper, Wiep

2013

Overview

Accumulation of aberrant proteins in inclusion bodies is a hallmark of many neurodegenerative diseases. Impairment of proteolytic systems is a common event in these protein misfolding diseases. Recently, mutations in the UBQLN 2 gene encoding ubiquilin 2 have been identified in X-linked amyotrophic lateral sclerosis (ALS). Furthermore, ubiquilin 2 is associated with inclusions in familial and sporadic ALS/dementia, synucleinopathies and polyglutamine diseases. Ubiquilin 2 exerts a regulatory role in proteostasis and thus it has been suggested that ubiquilin 2 pathology may be a common event in neurodegenerative diseases. Tauopathies, a heterogenous group of neurodegenerative diseases accompanied with dementia, are characterized by inclusions of the microtubule-binding protein tau. In the present study, we investigate whether ubiquilin 2 is connected with tau pathology in Alzheimer's disease (AD), supranuclear palsy (PSP) and Pick's disease (PiD) and familial cases with frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17). We show that ubiquilin 2 positive inclusions are absent in these tauopathies. Furthermore, we find decreased ubiquilin 2 protein levels in AD patients, but our results do not indicate a correlation with tau pathology. Our data show no evidence for involvement of ubiquilin 2 and indicate that other mechanisms underly the proteostatic disturbances in tauopathies.

• Publisher: Public Library of Science,Public Library of Science (PLoS)
• Subject: Aberration / Aged / Aged, 80 and over / Alzheimer's disease / Amyotrophic lateral sclerosis / Autophagy / Basal ganglia / Brain / Cell Cycle Proteins - metabolism / Cell Line, Tumor / Central nervous system diseases / Chromosome 17 / Dementia / Dementia disorders / Disease / Frontotemporal dementia / Genomes / Humans / Inclusion bodies / Inclusions / Middle Aged / Movement disorders / Mutation / Neurodegeneration / Neurodegenerative diseases / Neurodegenerative Diseases - metabolism / Neurodegenerative Diseases - pathology / Neurological diseases / Paralysis / Pathology / Polyglutamine diseases / Protein folding / Proteins / Proteolysis / Tau protein / tau Proteins - metabolism / Trinucleotide repeat diseases / Ubiquitins - metabolism