Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 1 de 1
Filter
Add more filters










Database
Language
Publication year range
1.
Sci Rep ; 14(1): 6049, 2024 03 13.
Article in English | MEDLINE | ID: mdl-38472280

ABSTRACT

The ubiquitin-adaptor protein UBQLN2 promotes degradation of several aggregate-prone proteins implicated in neurodegenerative diseases. Missense UBQLN2 mutations also cause X-linked amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD). Previously we demonstrated that the liquid-like properties of UBQLN2 molecular assemblies are altered by a specific pathogenic mutation, P506T, and that the propensity of UBQLN2 to aggregate correlated with neurotoxicity. Here, we systematically assess the effects of multiple, spatially distinct ALS/FTD-linked missense mutations on UBQLN2 aggregation propensity, neurotoxicity, phase separation, and autophagic flux. In contrast to what we observed for the P506T mutation, no other tested pathogenic mutant exhibited a clear correlation between aggregation propensity and neurotoxicity. These results emphasize the unique nature of pathogenic UBQLN2 mutations and argue against a generalizable link between aggregation propensity and neurodegeneration in UBQLN2-linked ALS/FTD.


Subject(s)
Amyotrophic Lateral Sclerosis , Frontotemporal Dementia , Humans , Frontotemporal Dementia/genetics , Amyotrophic Lateral Sclerosis/metabolism , Autophagy-Related Proteins/genetics , Mutation , Adaptor Proteins, Signal Transducing/metabolism
SELECTION OF CITATIONS
SEARCH DETAIL
...