Identification of miRNAs signature in association with neuropathophysiology in Alzheimer’s disease.
Lee, Mee Sim.
Date of Issue2013
School of Biological Sciences
National Neuroscience Institute
Cognition is typically attributed to neuronal development in brain. Aberrant cognitive performance becomes apparent with age and progressive neurodegenerative disorder such as Alzheimer’s disease (AD). Neuronal development in the adult brain can be modulated by complex microRNA (miRNA) regulatory network for structural and functional development of neurons and synapses. Our study aimed to identify and characterize biological function of miRNAs associated to AD neuropathophysiology. To identify a novel AD-associated miRNA signature, triple-transgenic (3xTg-AD) mouse model was first involved with immunohistochemical detection of AD neuropathophysiology such as deteriorated hippocampal neurogenesis and intraneuronal Aβ deposition. On the ensuing, profiling studies of neuronal miRNAs in 3xTg-AD mice were performed using SYBR Green-based real-time protocol. AD hippocampal response of mature miR-148b was significantly upregulated at 12 months of age. This study also expanded the repertoire of miRNA profiles in human blood mononuclear cells (BMC). Next, miRNA target identification via sequence-based approach and functional characterization through gene ontology analysis were achieved. Computational prediction approach unveiled the potential regulatory role of miR-148b in synaptic transmission via NPTN gene. This study advocates the functional link between miRNA regulatory network and AD neuropathology, which is instrumental for future miRNA studies on molecular neuropathogenesis of AD.
DRNTU::Science::Biological sciences::Human anatomy and physiology::Neurobiology
Final Year Project (FYP)
Nanyang Technological University