Peptidyl-Prolyl Isomerase 1 Regulates Protein Phosphatase 2A-Mediated Topographic Phosphorylation of Neurofilament Proteins

作者: H. C. Pant , P. Rudrabhatla , W. Albers

DOI: 10.1523/JNEUROSCI.4469-09.2009

关键词:

摘要: In normal neurons, neurofilament (NF) proteins are phosphorylated in the axonal compartment. However, neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's (PD), and amyotrophic lateral sclerosis (ALS), NF aberrantly hyperphosphorylated within cell bodies. The aberrant hyperphosphorylation of accumulations found neurodegeneration could be attributable to either deregulation proline-directed Ser/Thr kinase(s) activity or downregulation protein phosphatase(s) activity. this study, we that phosphatase 2A (PP2A) expression is high neuronal bodies inhibition PP2A by okadaic acid (OA), microcystin LR (mLR), fostriecin (Fos) leads perikaryal NF. Peptidyl-prolyl isomerase Pin1 inhibits dephosphorylation vitro. cortical modulates topographic phosphorylation residues tail domain inhibiting PP2A. Inhibition OA-induced Treatment neurons with OA Fos prevents general anterograde transport transfected green fluorescent protein–high-molecular-mass (NF-H) into axons caused NF-H, rescues effect. Furthermore, OA- Fos-induced apoptosis. We show a consequence independent c-Jun N-terminal kinase, extracellular signal-regulated cyclin-dependent kinase-5 pathways. This study highlights novel signaling role implicates therapeutic target reduce AD, PD, ALS.

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