Amyotrophic lateral sclerosis: the involvement of intracellular Ca2+ and protein kinase C

The neurodegenerative disease, amyotrophic lateral sclerosis (ALS), is characterized by the selective death of motoneurones and corticospinal tract neurones. Abnormalities in excitatory amino acids and their receptors, as well as disordered function of voltage-dependent [Ca.sup.2+] channels and superoxide dismutase have been reported in ALS patients. Furthermore, the activity of protein kinase C (PKC), a [Ca.sup.2]+, phospholipid-dependent enzyme, is also substantially increased in tissue from ALS patients, suggesting that alterations in intracellular free [Ca.sup.2+] may be central to many of the diverse pathogenic mechanisms potentially responsible for ALS as discussed here by Charles Krieger and colleagues. Increased PKC activity, in turn, may have direct or indirect effects on neuronal viability and influence the pathogenic process in ALS by modifying the phosphorylation of voltage-dependent [Ca.sup.2+] channels, neurotransmitter receptors and structural proteins.