Distinct partitioning of ALS associated TDP-43, FUS and SOD1 mutants into cellular inclusions
Natalie E Farrawell, Isabella A Lambert-Smith, Sadaf T Warraich, Ian P Blair, Darren N Saunders, Danny M Hatters, Justin J Yerbury
SCIENTIFIC REPORTS | NATURE PUBLISHING GROUP | Published : 2015
Amyotrophic lateral sclerosis is a rapidly progressing neurodegenerative disease associated with protein misfolding and aggregation. Most cases are characterized by TDP-43 positive inclusions, while a minority of familial ALS cases are instead FUS and SOD1 positive respectively. Cells can generate inclusions of variable type including previously characterized aggresomes, IPOD or JUNQ structures depending on the misfolded protein. SOD1 invariably forms JUNQ inclusions but it remains unclear whether other ALS protein aggregates arise as one of these previously described inclusion types or form unique structures. Here we show that FUS variably partitioned to IPOD, JUNQ or alternate structures, ..View full abstract
Awarded by NHMRC project
JJY is supported by the ARC in the form of a Discovery Early Career award, NHMRC project grant 1003032, and an MNDRIA grant in aid. DMH is supported by an ARC Future Fellowship, an ARC Discovery grant and NHMRC project grants. DNS is supported by NHMRC project grants. Tissues were received from the New South Wales Brain Banks and Queensland Brain Bank (Australian Brain Bank Network). IPB is supported by an MND Australia Leadership Grant.