Fig. P1.

Induction of motor neuron death by nitrated Hsp90. Many types of stress, including deprivation of growth factors and exposure to nitric oxide in cells that express mutant SOD, result in the endogenous production of ONOO⁻. Nitration of either of two tyrosine residues on the prosurvival protein Hsp90 is sufficient to activate a gain of function that makes the protein toxic. The activation of the P2X7 receptor by nitrated Hsp90 results in an influx of calcium that mobilizes FasL to the plasma membrane and activates the FADD-mediated Fas pathway. These events culminate in cell death by apoptosis.