| First Author | Rutherford NJ | Year | 2013 |
| Journal | Brain Res | Volume | 1524 |
| Pages | 62-73 | PubMed ID | 23774650 |
| Mgi Jnum | J:310933 | Mgi Id | MGI:6762608 |
| Doi | 10.1016/j.brainres.2013.06.006 | Citation | Rutherford NJ, et al. (2013) Unbiased screen reveals ubiquilin-1 and -2 highly associated with huntingtin inclusions. Brain Res 1524:62-73 |
| abstractText | Recently mutations in ubiquilin-2 were identified in patients with amyotrophic lateral sclerosis (ALS) and ALS/dementia providing direct evidence for the importance of this protein in neurodegenerative diseases. Histological studies have suggested that ubiquilin-1/-2 are associated with various pathological inclusions including Lewy bodies in Parkinson's disease, neurofibrillary tangles in Alzheimer's disease, polyQ inclusions in expansion repeat diseases and various proteinopathies associated with ALS and frontotemporal dementia. Using specific ubiquilin-2 antibodies and a series of transgenic mouse models of proteinopathies associated with neurodegenerative disease, we show that ubiquilin-2 preferentially associates with huntingtin polyQ expansion aggregates compared to alpha-synuclein, tau and several other types of protein inclusions. These results were confirmed by similar findings for ubiquilin-1 and -2 in human brain tissue sections, where accumulation was observed in huntingtin inclusions, but only infrequently in other types of protein inclusions. In cultured cells, ubiquilin-2 associates with huntingtin/polyQ aggregates, but this is not compromised by disease-causing mutations. Although ubiquilin proteins can function as chaperones to shuttle proteins for degradation, there is persistent co-localization between ubiquilin-2 and polyQ aggregated proteins during disease progression in the N586-82Q-C63 Huntington's disease mouse model. Thus, the co-localization of ubiquilin-2 with the huntingtin aggregates does not appear to facilitate aggregate removal. |
