UNASSIGNED: @entity746 ( @entity746 ) is a @entity179 characterised by the progressive @entity75 and spinal cord motor neurons. @entity4903 and oxidative stress have been implicated in @entity746 pathogenesis. However, it is unknown whether the defects in these pathways extend to non-neuronal tissues such as fibroblasts. Fibroblasts, unlike neuronal tissue, are readily available and may hold potential for short-term, rapid diagnostic and prognostic purposes. We investigated whether primary skin fibroblasts from @entity746 @entity1 share, or can be manipulated to develop, functional and pathological abnormalities seen in affected neuronal cells. We inhibited UPS function and induced oxidative stress in the fibroblasts and found that @entity746 -related cellular changes, such as aggregate formation and ubiquitination of @entity746 -associated proteins ( @entity529 and @entity69255 ), can be reproduced in these cells. Higher levels of @entity529 ubiquitination, as evident by colocalization between @entity529 and ubiquitin, were found in all six @entity746 cases compared to controls following extracellular insults. In contrast, colocalization between @entity69255 and ubiquitin was not markedly different between @entity746 cases and control. A UPS reporter assay revealed @entity3002 in @entity1 fibroblasts. Despite the presence of @entity746 -related cellular changes in the @entity1 fibroblasts, no elevated @entity137 was observed. This suggests that aggregate formation and colocalization of @entity746 -associated proteins may be insufficient alone to confer @entity137 in fibroblasts used in the present study. Chronic exposure to @entity746 -linked stresses and the @entity746 -linked cellular pathologies may be necessary to breach an unknown threshold that triggers cell death.

Evaluation of Skin Fibroblasts from Amyotrophic Lateral Sclerosis XXXX for the Rapid Study of Pathological Features.

@entity1 :: ('9606', 'Species') :: ['patients', 'patient'] @entity137 :: ('MESH:D064420', 'Disease') :: ['toxicity'] @entity75 :: ('MESH:D001927', 'Disease') :: ['degeneration of brain'] @entity3002 :: ('MESH:D009421', 'Disease') :: ['UPS abnormalities'] @entity179 :: ('MESH:D019636', 'Disease') :: ['fatal neurodegenerative disorder'] @entity746 :: ('MESH:D000690', 'Disease') :: ['ALS', 'Amyotrophic lateral sclerosis'] @entity529 :: ('23435', 'Gene') :: ['TDP-43'] @entity69255 :: ('29978', 'Gene') :: ['ubiquilin 2'] @entity4903 :: ('MESH:D004700', 'Disease') :: ['Ubiquitin-proteasome system (UPS) dysfunction']
@entity1 :: (9606,Species) :: ['Patients']
