ANALYSIS OF FUNCTION OF HUMAN BRAIN CARBOXYPEPTIDASE B-SPECIFIC C14-MODULE

点击翻译按钮获取中文摘要

To clarify a pathophysiological significance of human brain carboxypeptidase B (HBCPB), the specific C-terminal region, C14-moduIe, was analyzed by (1) morphological and (2) molecular-bioc hemical analyses.(1) Through comparative analysis between five cases of sporadic Alzheimer's disease patients and normal aged, the following morphological novel findings were obtained. HBCPB expression in neuronal perikarya, which was already identified as endoplasmic reticulum, was analyzed throughout neurons. In all normal brains, HBCPB is expressed in restricted neurons including highly vulnerable neurons in Alzheimer's disease such as hippocampal pyramidal neuron and also in uninvolved neurons such as lateral geniculate body neurons. In all five Alzheimer's brains analyzed, however, HBCPB expression in hippocampal pyramidal neurons, but not in lateral genicu late body neurons, were significantly decreased. Selective decrease in expressed amount and nonhomogeneous expression pattern in endoplasmic reticulum in all Alzheimer's cases indicate that neuron-specific inhibition of HBCPB expression is of pathophysiological significance in progress ion of Alzheimer's disease.(2) By epitope analysis of HBCPB-C14-module using anti C14-module antibody, it was clarified that the module is composed of two epitopes (each 7- amino' acid residues), EP1 and EP2. The former epitope is highly independent, and an rabbit antibody was raised against EPI peptides (anti C14-EP1). In the exoproteolytic analysis of synthetic Aβ1-42 by HBCPB, both co-existence of EPI peptide or anti C14-EP1 antibody inhibited the reaction.Taken together, it was clarified that functional analysis of HBCPB by focusing on C14-module is important, and a substantial background was establ ished to understand the significance of HBCPB as therapeutical target for Alzheimer's disease.