Phosphorylation of eukaryotic initiation factor-2α (eIF2α)... : NeuroReport (original) (raw)
Clinical Neuroscience And Neuropathology
Phosphorylation of eukaryotic initiation factor-2α (eIF2α) is associated with neuronal degeneration in Alzheimer's disease
Chang, Raymond C. C.1 2; Wong, Ada K. Y.1; Ng, Ho-Keung3; Hugon, Jacques1 2 CA
1Department of Anatomy, Faculty of Medicine
2Central Laboratory of the Institute of Molecular Technology for Drug Discovery and Synthesis, The University of Hong Kong, Laboratory Block, Faculty of Medicine Building, 21 Sassoon Road, Pokfulam
3Department of Anatomical and Cellular Pathology, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong SAR
CA,1Corresponding Author and Address: [email protected]
Received 11 October 2002; accepted 11 October 2002
Abstract
Inhibition of protein translation is a mode of inducing neuronal apoptosis and neurodegeneration in Alzheimer's disease (AD). Phosphorylation of eukaryotic initiation factor-2α (eIF2α) terminates global protein translation and induces apoptosis. We examined whether this signaling pathway occurs in degenerating neurons of AD. Brain sections from young individuals, age-matched control individuals and AD patients were examined for immunoreactivity of phosphorylated eIF2α by immunohistochemical analysis. While young brain sections did not display and age-matched brain sections have mild immunoreactive positive cells, AD brain sections revealed intense immunoreactivity for phosphorylated eIF2α. Most of the phosphorylated eIF2α immunoreactive positive neurons have high immunoreactivity for phosphorylated tau using AT8 antibody. Also, intense staining of phosphorylated eIF2α is associated vacuoles in degenerating neurons. This phenomenon was also observed for the immunohistochemical staining of phosphorylated PKR (double-stranded RNA-dependent protein kinase), the upstream kinase for eIF2α. Activation of PKR-eIF2α pathway is considered to be pro-apoptotic. In addition, formation of autophagy is regulated by eIF2α kinase. Therefore, it is concluded that phosphorylation of eIF2α is associated with the degeneration of neurons in AD.
© 2002 Lippincott Williams & Wilkins, Inc.