Protein kinase C-mediated protection of motoneurons from excitotoxicity

Amyotrophic lateral sclerosis (ALS) is a progressive motoneuron disease, whose pathogenesis remains unclear. Phorbol 12-myristate 13-acetate (PMA) has been shown to be neurotrophic and neuroprotective in several types of neurons in culture. However, the survival effect of PMA on motoneurons has not been reported. Therefore, we investigated this using purified rat motoneurons. PMA showed a small but significant neurotrophic activity, which was inhibited by GF109203X, a protein kinase C (PKC) inhibitor. Under the conditions in which the survival of motoneurons is supported by brain-derived neurotrophic factor (BDNF), excitotoxicity was induced by glutamate. PMA markedly protected motoneurons against excitotoxicity. The up-regulation of PKC in the spinal cord of ALS patients was previously reported, therefore, the present results indicate that PKC activation might be involved in neuroprotection.