Role of NMNAT2 regulation in cortical primary neurons

Konstantoulaki, Katerina (2019) Role of NMNAT2 regulation in cortical primary neurons. MRes thesis, University of Nottingham.

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Abstract

Nicotinamide mononucleotide adenylyl transferase 2 (NMNAT2) is a key neuronal maintenance factor which provides potent neuroprotec-tion in several models of neurological disorders. NMNAT2 is significantly reduced in Alzheimer’s, Huntington’s, Parkinson’s diseases.

MicroRNAs have emerged as key regulators of biological processes in animals. The microRNA system is part of the cell’s epigenetic arsenal that shapes the formation and tight regulation of gene networks during the establishment and the remodelling of the brain by controlling both levels and translation of messenger RNA. Deregulation of miRNA func-tion is associated with a plethora of human diseases and they are con-sidered a key molecular tool for the diagnosis and prognosis of human diseases. Up to date, NMNAT2 regulation by microRNAs has not been investigated.

Here we investigate NMNAT2 role in axonal growth of primary cortical neurons. Consequently, we identify four putative miRNAs that target NMNAT2 and study their effect on axonal growth and NMNAT2 mRNA expression. We identify miR-129-3p as a regulator of NMNAT2 in cortical neurons as it both limits their axonal length and reduces the mRNA lev-els of NMNAT2.

Understanding microRNA regulation of NMNAT2 can build a strong momentum to encourage studies of miRNAs as molecular tools for the diagnosis and prognosis of NMNAT2 related pathologies as long as mechanistic studies to develop microRNA-targeted therapies.

Item Type: Thesis (University of Nottingham only) (MRes)
Supervisors: Dajas-Bailador, Federico
Keywords: nmnat2, Neurons, Degeneration, Neuronal degeneration, Wallerian degeneration, Axons, Axonal degeneration, Neurodegeneration, microRNA, miRNA, Cortical, Cortical neurons, n2a
Subjects: R Medicine > RC Internal medicine > RC 321 Neuroscience. Biological psychiatry. Neuropsychiatry
Faculties/Schools: UK Campuses > Faculty of Medicine and Health Sciences > School of Life Sciences
Item ID: 56823
Depositing User: Konstantoulaki, Aikaterini
Date Deposited: 21 Oct 2019 07:40
Last Modified: 06 May 2020 13:47
URI: http://eprints.nottingham.ac.uk/id/eprint/56823

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