Fig. 3.
Role of FasL, Fas, p38 kinase, and nNOS in mutant SOD1 motoneuron death. (A–D) Mutant SOD1 motoneurons were treated (or not treated) at 1 DIV with Detanonoate (A and B) or agonistic anti-Fas antibodies (C and D). Cell survival was quantified at 3 DIV by phase-contrast microscopy and expressed relative to the number of motoneurons alive under basal conditions (0). Addition of the extracellular part of Fas receptor, Fas-Fc, the p38 kinase inhibitor SB203580 (5 μM), or the nNOS inhibitor L-VNIO (10 μM) significantly reduced the NO-triggered death of SOD1G85R (A) or SOD1G93A (B) motoneurons. Mutant SOD1 motoneuron death mediated by agonistic anti-Fas antibodies at 0.5 ng/ml or 100 ng/ml was prevented or significantly reduced by Fas-Fc. Error bars show SEM. ∗, P < 0.05; ∗∗, P < 0.01; ∗∗∗, P < 0.001, Student's t test. (E) Model illustrating the Fas/NO feedback loop in mutant SOD1 motoneurons.