Expression of calbindin-D-28K in motoneuron hybrid cells after retroviral infection with calbindin-D-28K cDNA prevents amyotrophic lateral sclerosis IgG-mediated cytotoxicity

Calbindin-D-28K and/or parvalbumin appear to influence the selective vulnerability of motoneurons In amyotrophic lateral sclerosis (ALS). Their immunoreactivity is undetectable in motoneurons readily damaged in human ALS, and in differentiated motoneuron hybrid cells [ventral spinal cord (VSC 4.1 cells)] that undergo calcium-dependent apoptotic cell death in the presence of ALS immunoglobulins. To provide additional evidence for the role of calcium-binding proteins in motoneuron vulnerability, VSC 4.1 cells were Infected with a retrovirus carrying calbindin-D-28K cDNA under the control of the promoter of the phosphoglycerate kinase gene, Differentiated calbindin-D-28K cDNA-infected cells expressed high calbindin-D-28K and demonstrated increased resistance to ALS IgG-mediated toxicity, Treatment with calbindin-D-28K antisense oligodeoxynucleotides, which significantly decreased calbindin-D-28K expression, rendered these cells vulnerable again to ALS Ige toxicity.