phosphatidylinositol transfer protein α-dependent survival factor protects cultured primary neurons against serum deprivation-induced cell death

Selective neuronal loss is a prominent feature in both acute and chronic neurological disorders. Recently, a link between neurodegeneration and a deficiency in the lipid transport protein phosphatidylinositol transfer protein α (PI-TPα) has been demonstrated. In this context it may be of importance that fibroblasts overexpressing PI-TPα are known to produce and secrete bioactive survival factors that protect fibroblasts against UV-induced apoptosis. In the present study it was investigated whether the conditioned medium of cells overexpressing PI-TPα (CMα) has neuroprotective effects on primary neurons in culture. We show that CMα is capable of protecting primary, spinal cord-derived motor neurons from serum deprivation-induced cell death. Since the conditioned medium of wild-type cells was much less effective, we infer that the neuroprotective effect of CMα is linked (in part) to the PI-TPα-dependent production of arachidonic acid metabolites. The neuroprotective activity of CMα is partly inhibited by suramin, a broad-spectrum antagonist of G-protein coupled receptors. Western blot analysis shows that brain cortex and spinal cord express relatively high levels of PI-TPα, suggesting that the survival factor may be produced in neuronal tissue. We propose that the bioactive survival factor is implicated in neuronal survival. If so, PI-TPα could be a promising target to be evaluated in studies on the prevention and treatment of neurological disorders.