Involvement of FUS in cell cycle regulation and ALS pathogenesis

Fused in sarcoma/traslocated in liposarcoma (FUS/TLS) is an RNA/ DNA binding protein; mutations in the coding region of FUS, which cause the retention of the protein in the cytoplasm, have been found associated with ALS. Literature data demonstrated that also mutations in the 3’UTR, which result in overexpressed FUS-WT, are involved in the onset of the disease. In light of its well recognised role in ALS pathology we investigated its function in nervous system development. We derived mouse neural progenitor cells (NPC) from foetal spinal cord in which we overexpressed human wild type (hFUS-WT) or mutated (hFUS-P525L) FUS, which has been found in one of the most aggressive forms of juvenile ALS. The expression of the cell cyle regulators p27 and cdk2 is modulated in cells overexpressing hFUS-WT, suggesting that FUS interferes with cell cycle progression. Accordingly, cyto uorimetric analysis and BrdU immunolocalization show a G1 arrest of cell proliferation between 48 and 72hrs. We are currently investigating the effect of the overexpression of hFUS- P525L mutated form on cell cycl