Elevated Cytosolic Phospholipase A2α as a Target for Treatment and Prevention the Progression of Neurodegenerative Diseases

Rachel Levy, Yulia Solomonov, Kesenia Kasianov, Yafa Malada-Edelstein, Nurit Hadad

Research output: Chapter in Book/Report/Conference proceedingChapterpeer-review

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 languageEnglish
Title of host publicationAdvanced Studies in Experimental and Clinical Medicine
Subtitle of host publicationModern Trends and Latest Approaches
EditorsP. Mereena Luke, K. R. Dhanya, Didier Rouxel
PublisherTaylor & Francis Group
Pages159-165
Number of pages7
ISBN (Electronic)9781003057451
ISBN (Print)9781771889063, 9781774637708
DOIs
StatePublished - Mar 2021

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