Characterization of Cathepsins E and D Accumulated at Early Stages of Neuronal Damage in Hippocampal Neurons of Rats

Abstract

Excitatory amino acid-mediated excitotoxic damage has been implicated in the pathogenesis of a variety of acute and chronic neurodegenerative diseases including stroke, trauma, epilepsy and Alzheimer’s disease (for reviews see: 1,2). Despite the clinical importance, the understanding of subcellular mechanism of excitotoxic neuronal cell death is limited. There is increasing evidence that calcium-activated enzymes such as phospholipases, protein kinases, endonucleases or non-lysosomal proteinases play a pivotal role in the excitotoxic neuronal cell death. Among these candidates, the activation of calpain, a calcium-activated cysteine proteinase, has been widely accepted as an important factor contributing to excitotoxic neuronal cell death (3,4). However, little is known about the role of other non-lysosomal proteolytic systems. Recently we have suggested that cathepsin E, a non-lysosomal aspartic proteinase, is associated with the pathological process of ischemia (5) and normal aging (6). Thus it is of special interest whether cathepsin E is involved in the process of excitotoxic neuronal cell death. Here we report evidence indicating that cathepsin E as well as cathepsin D, a lysosomal aspartic proteinase, is closely related to the neuronal cell death in the CA3 subfield of rat hippocampus induced by intraventricular injection of kainate, a potent glutamate agonist.