G93A SOD1 alters cell cycle in a cellular model of Amyotrophic Lateral Sclerosis.
Amyotrophic Lateral Sclerosis (ALS) is a neurodegenerative multifactorial disease characterized, like other diseases such as Alzheimer's disease (AD), Parkinson's disease (PD) or frontotemporal dementia (FTD), by the degeneration of specific neuronal cell populations. Motor neuron loss is distinctive of ALS. However, the causes of onset and progression of motor neuron death are still largely unknown. In about 2% of all cases, mutations in the gene encoding for the Cu/Zn superoxide dismutase (SOD1) are implicated in the disease. Several alterations in the expression or activation of cell cycle proteins have been described in the neurodegenerative diseases and related to cell death. In this work we show that mutant SOD1 can alter cell cycle in a cellular model of ALS. Our findings suggest that modifications in the cell cycle progression could be due to an increased interaction between mutant G93A SOD1 and Bcl-2 through the cyclins regulator p27. As previously described in post mitotic neurons, cell cycle alterations could fatally lead to cell death.
Cova
Emanuela
E
Laboratory of Experimental Neurobiology, IRCCS, National Neurological Institute C. Mondino, Via Mondino, 2, 27100 Pavia, Italy. emanuela.cova@mondino.it
Ghiroldi
Andrea
A
Guareschi
Stefania
S
Mazzini
Giuliano
G
Gagliardi
Stella
S
Davin
Annalisa
A
Bianchi
Marika
M
Ceroni
Mauro
M
Cereda
Cristina
C
D019943:Amino Acid Substitution; D000690:Amyotrophic Lateral Sclerosis / Q000235:genetics* / Q000378:metabolism; D002453:Cell Cycle; D002460:Cell Line; D049109:Cell Proliferation; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D017354:Point Mutation; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D050777:Stathmin / Q000378:metabolism; D013482:Superoxide Dismutase / Q000235:genetics* / Q000378:metabolism; D000072105:Superoxide Dismutase-1
D019253:Proto-Oncogene Proteins c-bcl-2; C000606290:SOD1 protein, human; D050777:Stathmin; D050760:Cyclin-Dependent Kinase Inhibitor p27; C109415:SOD1 G93A protein; D013482:Superoxide Dismutase; D000072105:Superoxide Dismutase-1