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Investigating UBA1 distribution and its relevance to Spinal Muscular Atrophy
Author(s) -
Maani Amr,
Shorrock Hannah,
Gillingwater Tom
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.744.5
Subject(s) - sma* , spinal muscular atrophy , smn1 , neuroscience , medicine , biology , computer science , algorithm
Spinal muscular atrophy (SMA) is an autosomal recessive neurodegenerative disease characterized by the degeneration of lower motor neurons. SMA is the most common genetic cause of infant mortality and is caused by a homozygous deletion of the Survival Motor Neuron 1 gene (SMN1). There is currently no effective therapy. However, experiments on animal models targeting UBA1 pathways have shown improvements in neuromuscular phenotype. Studies have shown that there is a reduction of UBA1 in SMA and that mutations in UBA1 can cause X‐linked SMA. Nevertheless, the mechanism by which UBA1 mediates degeneration in SMA is unclear. This project investigated the role of UBA1 in SMA and, more specifically, the relevance of sub‐cellular UBA1 distribution in SMA. UBA1 distribution in post‐mitotic cells, including cultured primary neurons, was studied to identify whether UBA1 distribution is disrupted in cell models of SMA. UBA1 distribution was also studied in HEK293 cells to confirm the distribution in dividing cells. This study confirmed that UBA1 distribution changes over time in cultured motor neurons and that there is a reduction of nuclear UBA1 in SMA motor neurons. Results suggest that understanding UBA1 distribution in SMA will be essential to future studies in reaching a therapeutic cure. Support or Funding Information The University of Edinburgh