Please use this identifier to cite or link to this item: https://scholarbank.nus.edu.sg/handle/10635/124205
Title: AN ISOFORM-SPECIFIC ROLE OF FYNT IN ALZHEIMER'S DISEASE AND ITS RELEVANCE IN NEUROINFLAMMATION
Authors: LEE CHING LI
Keywords: Fyn tyrosine kinase, FynT, Alzheimer's disease, Neuroinflammation, Astrocytes
Issue Date: 22-Jan-2016
Citation: LEE CHING LI (2016-01-22). AN ISOFORM-SPECIFIC ROLE OF FYNT IN ALZHEIMER'S DISEASE AND ITS RELEVANCE IN NEUROINFLAMMATION. ScholarBank@NUS Repository.
Abstract: FYN IS IMPLICATED IN THE PATHOGENESIS OF ALZHEIMER?S DISEASE (AD), MEDIATING AMYLOID-BETA TOXICITY AND TAU HYPERPHOSPHORYLATION. HOWEVER, NO STUDY HAS ATTEMPTED TO DELINEATE ISOFORM-SPECIFIC ROLES OF FYN IN ASSOCIATION WITH AD. OUR PRELIMINARY DATA OF EXON ARRAY DEMONSTRATED DIFFERENTIAL ALTERNATIVE SPLICING OF FYN IN AD, WITH SIGNIFICANT INCREASE OF FYNT BUT NO CHANGE OF BRAIN-PREDOMINANT FYNB IN AD. THIS THESIS AIMS TO IDENTIFY AN ISOFORM-SPECIFIC ROLE OF FYNT IN AD AND THE POSSIBLE IMPACT OF FYNT INDUCTION IN THE DISEASE. STUDIES ON POST-MORTEM AD BRAINS AND PRIMARY CORTICAL CULTURES DEMONSTRATED THAT FYNT INDUCTION WAS INDEPENDENTLY ASSOCIATED WITH NEUROFIBRILLARY DEGENERATION AND REACTIVE ASTROGLIOSIS. FURTHERMORE, WE OBSERVED THAT TNFA-INDUCED FYNT, BUT NOT FYNB IN PRIMARY ASTROCYTES. USING RECOMBINANT FYNT MUTANT APPROACHES, FYNT KINASE ACTIVITY WAS FOUND TO FACILITATE TNFA-INDUCED INFLAMMATORY RESPONSES IN IMMORTALIZED NORMAL HUMAN ASTROCYTES, LIKELY ASSOCIATED WITH NF-KB SIGN
URI: http://scholarbank.nus.edu.sg/handle/10635/124205
Appears in Collections:Ph.D Theses (Open)

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