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Apoptosis in amyotrophic lateral sclerosis—what is the evidence?

2005; Elsevier BV; Volume: 4; Issue: 8 Linguagem: Inglês

10.1016/s1474-4422(05)70142-3

1474-4465

Sivakumar Sathasivam, Pamela J. Shaw,

Nuclear Receptors and Signaling

There is increasing evidence that a programmed mechanism of cell death resembling apoptosis is responsible for motor-neuron degeneration in amyotrophic lateral sclerosis. Our understanding of the cell-death pathway has come from studies of both experimental models and human tissue. Here we examine in detail the in vitro and in vivo evidence for and against apoptosis in amyotrophic lateral sclerosis, looking at morphological changes, caspase activation, alterations in Bcl-2 oncoproteins, involvement of death receptors, expression of apoptosis-related molecules, and the role of the p53 pathway. Finally, we present evidence of potential therapeutic agents that could modulate the apoptotic pathway in amyotrophic lateral sclerosis and slow disease progression.