Biology of 14-3 3 proteins regulating neuronal cell death

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We aimed in this study to elucidate the biological mechanisms regulating neuronal cell death and molecular interactions affecting the neurological diseases in children on both aspects, biological and clinical medicines.Detection of 14-3-3 protein in the CSF is a powerful tool for elucidating the underlying mechanisms of neurological disorders. There have been useful studies on 14-3-3 CSF protein detection in Creutzfeldt-Jakob disease and other neurological disorders, but none on cerebellar diseases. To evaluate detection of 14-3-3 protein in the CSF of patients with cerebellar diseases, we examined 14-3-3 protein in the CSF by immunoblotting in seven patients with cerebellar diseases, i.e., acute cerebellitis (2), acute cerebellar ataxia (2), and cerebellar atrophy (3). 14-3-3 protein isoforms were also identified by means of isoform-specific antibodies. 14-3-3 protein was detected in the CSF of six patients, the exception being one with acute cerebellar ataxia. Interestingly, only the … More 14-3-3 c isoform was detected throughout in 14-3-3 positive patients. Moreover, longitudinal analysis of 14-3-3 CSF protein in one patient with cerebellar atrophy showed that the 14-3-3 band density proportionally decreased when the cerebellar atrophy gradually progressed. We concluded that 14-3-3 protein in the CSF is a significant cerebellar destructive marker as well as one in other brain diseases, and the unique detection of 14-3-3 ε may indicate cerebellar involvement in the brain.Since 14-3-3 proteins are an intimate partner of apoptosis signal-regulating kinase 1 (ASK1), we examined in vitro protein kinse assay using recombinant ASK1 and 14-3-3 proteins. We clearly showed that ASK1 can phosphorylate 14-3-3 proteins with several portions of serine and threonine residues. Interestingly, phosphorylated 14-3-3 proteins diminished ASK1 autophosphorylation, suggesting that ASK1-14-3-3 proteins interaction may influence the kinetic activity of ASK1. As 14-3-3 proteins bind to ASK1 using a binding consensus motif, protein-protein interaction is supposed to be critical biological function on both ASK1 and 14-3-3 proteins. (305 words) Less