EFFECT OF CILIARY NEUROTROPHIC FACTOR ON /3-AMYWID PRECURSOR PROTEIN mRNA EXPRESSION

The neuropathological hallmark of Alzheimer's disease is the progressive accumulation of senile plaques. The major constituent of senile plaques is amyloid /3/ A4 protein. This p/ A4 peptide consists of 42-43 amino acids and is derived from a large transmembrane protein, the p-amyloid precursor protein (APP). 5 The APP gene is expressed in various tissues and is highly conserved in evolution. In addition, three major isoforms (APP695, APP751, APP770) are generated from a single gene by alternative splicing, two of which (APP75l,APP770) contain the Kunitz-type protease inhibitor (KPI) domain. APP is presumed to play an important role in physiological or pathological conditions. However, the mechanisms regulating APP are yet unknown. Ciliary neurotrophic factor (CNTF) is a potent neurotrophic factor that can regulate the survival of cultured presympathetic, sympathetic, sensory, 1 spinal motor neurons and hippocampal neurons. 2 Previous studies suggest that secreted forms of APPs have trophic activities for cerebral cortical neurons. 3 In order to identify the factors that regulate APP gene expressions, we studied the effect of CNTF on APP mRNA expression in cultured neuroblastoma and glioma cells.