Abstract
Intravenous injections of an antisense against the main pro-inflammatory enzyme; cytosolic phospholipase A2α (cPLA2α) reduced cPLA2α upregulation specifically at the site of inflammation. To study the role of cPLA2α in neurodegenerative diseases a specific antisense against cPLA2α (AS) was brain infused to inhibit cPLA2α upregulation in the brain. Brain infusion of the antisense drug in a mouse model of amyloid brain infusion, representing a mouse model of Alzheimer’s disease (AD), was found to be efficacious in preventing cPLA2α upregulation in the brain and in the prevention of the disease. Reduction of the elevated expression of cPLA2α in the spinal cord of human SOD1G93A transgenic (hmSOD1) mice (a mouse model for amyotrophic lateral sclerosis (ALS)) by brain infusion of AS at week 15 (shortly before the appearance of the disease symptoms) for a duration of 6 weeks, delayed the loss of motor neuron function in comparison with hmSOD1 mice and with sense brain infused hmSOD1 mice. Since specific reduction of cPLA2α in the brain and spinal cord significantly attenuated the development of the diseases in mouse models of AD and ALS, cPLA2α may offer an efficient target for treatment neurodegenerative diseases.
Original language | English |
---|---|
Title of host publication | Advanced Studies in Experimental and Clinical Medicine |
Subtitle of host publication | Modern Trends and Latest Approaches |
Editors | P. Mereena Luke, K. R. Dhanya, Didier Rouxel |
Publisher | Taylor & Francis Group |
Pages | 159-165 |
Number of pages | 7 |
ISBN (Electronic) | 9781003057451 |
ISBN (Print) | 9781771889063, 9781774637708 |
DOIs | |
State | Published - Mar 2021 |