TDP43-FUS Cell Line

Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder characterized by loss of both upper and lower motoneurons in the brain and the spinal cord. ALS and other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s disease; are characterized by defects in protein processing resulting in protein misfolding, mislocalization and also inclusion formation in motor neurons. Classical neuropathological hallmarks of ALS include ubiquitinated inclusions containing the disordered TDP-43 and FUS proteins; although pathology can be heterogeneous with the appearance of other protein aggregates. Mutations in more than forty genes have been reported to associate with ALS. TDP-43 is a highly-conserved, ubiquitously-expressed ribonucleoprotein with multiple roles in nucleic acid metabolism. TDP-43 mainly resides in the nucleus. However, under pathological conditions, TDP-43 mislocalizes to the cytosol. TDP-43 has been identified as one of the primary component of ubiquitinated and hyper-phosphorylated cytosolic aggregates observed in ALS patients. TDP-43 is related with both familial and sporadic forms of ALS and its aggregation is considered a hallmark of ALS as it is observed in approximately 97% of all ALS patients regardless of the mechanisms of disease onset. Fused in sarcoma (FUS) is a multifunctional RNA-binding protein that plays a role in many RNA metabolism pathways. FUS is genetically and pathologically linked to uncommon but very aggressive forms of ALS and frontotemporal dementia (FTD). As TDP-43, FUS is mainly localized in the nucleus and under pathological conditions it is aggregated in the cytosol. To date, more than 50 different FUS mutations have been identified in patients with ALS, which together account for approximately 4% of familial cases and fewer than 2% of patients with sporadic ALS.