Pattern of ubiquilin pathology in ALS and FTLD indicates presence of C9ORF72 hexanucleotide expansion

…, JL Robinson, L Kwong, EB Lee, YO Ali, N Safren… - Acta …, 2012 - Springer
C9ORF72-hexanucleotide repeat expansions and ubiquilin-2 (UBQLN2) mutations are
recently identified genetic markers in amyotrophic lateral sclerosis (ALS) and frontotemporal …

[HTML][HTML] Abnormal RNA stability in amyotrophic lateral sclerosis

…, HC Archbold, X Li, K Weskamp, N Safren… - Nature …, 2018 - nature.com
Amyotrophic lateral sclerosis (ALS) and frontotemporal dementia (FTD) share key features,
including accumulation of the RNA-binding protein TDP-43. TDP-43 regulates RNA …

Motor neuron disease, TDP-43 pathology, and memory deficits in mice expressing ALS–FTD-linked UBQLN2 mutations

…, I Kovlyagina, P Georgiou, N Safren… - Proceedings of the …, 2016 - National Acad Sciences
Missense mutations in ubiquilin 2 (UBQLN2) cause ALS with frontotemporal dementia (ALS–FTD).
Animal models of ALS are useful for understanding the mechanisms of pathogenesis …

Mutant UBQLN2 promotes toxicity by modulating intrinsic self-assembly

LM Sharkey, N Safren, AS Pithadia… - Proceedings of the …, 2018 - National Acad Sciences
UBQLN2 is one of a family of proteins implicated in ubiquitin-dependent protein quality
control and integrally tied to human neurodegenerative disease. Whereas wild-type UBQLN2 …

The proline/arginine dipeptide from hexanucleotide repeat expanded C9ORF72 inhibits the proteasome

…, M Lan, J Mojsilovic-Petrovic, WH Choi, N Safren… - Eneuro, 2017 - eneuro.org
An intronic hexanucleotide repeat expansion (HRE) mutation in the C9ORF72 gene is the
most common cause of familial ALS and frontotemporal dementia (FTD) and is found in ∼7% …

Inhibition of PIP4Kγ ameliorates the pathological effects of mutant huntingtin protein

…, SSP Giridharan, YC Chen, S Patnaik, N Safren… - elife, 2017 - elifesciences.org
10.7554/eLife.29123.001 The discovery of the causative gene for Huntington’s disease (HD)
has promoted numerous efforts to uncover cellular pathways that lower levels of mutant …

[HTML][HTML] Pathogenic mutations in UBQLN2 exhibit diverse aggregation propensity and neurotoxicity

N Safren, TP Dao, HM Mohan, C Huang, B Trotter… - Scientific reports, 2024 - nature.com
The ubiquitin-adaptor protein UBQLN2 promotes degradation of several aggregate-prone
proteins implicated in neurodegenerative diseases. Missense UBQLN2 mutations also cause …

[HTML][HTML] Ubiquilin-1 overexpression increases the lifespan and delays accumulation of Huntingtin aggregates in the R6/2 mouse model of Huntington's disease

N Safren, A El Ayadi, L Chang, CE Terrillion, TD Gould… - PloS one, 2014 - journals.plos.org
Huntington's Disease (HD) is a neurodegenerative disorder that is caused by abnormal
expansion of a polyglutamine tract in huntingtin (htt) protein. The expansion leads to increased …

Monitoring neuronal survival via longitudinal fluorescence microscopy

K Weskamp, N Safren, R Miguez… - JoVE (Journal of Visualized …, 2019 - jove.com
Standard cytotoxicity assays, which require the collection of lysates or fixed cells at multiple
time points, have limited sensitivity and capacity to assess factors that influence neuronal fate…

Ubiquilin-2 differentially regulates polyglutamine disease proteins

JE Gerson, N Safren, S Fischer, R Patel… - Human molecular …, 2020 - academic.oup.com
Divergent protein context helps explain why polyglutamine expansion diseases differ clinically
and pathologically. This heterogeneity may also extend to how polyglutamine disease …