Role of NMNAT2 regulation in cortical primary neurons

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 r...

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Main Author: Konstantoulaki, Katerina
Format: Thesis (University of Nottingham only)
Language:English
Published: 2019
Subjects:
Online Access:https://eprints.nottingham.ac.uk/56823/
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author Konstantoulaki, Katerina
author_facet Konstantoulaki, Katerina
author_sort Konstantoulaki, Katerina
building Nottingham Research Data Repository
collection Online Access
description 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.
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spelling nottingham-568232025-02-28T12:13:23Z https://eprints.nottingham.ac.uk/56823/ Role of NMNAT2 regulation in cortical primary neurons Konstantoulaki, Katerina 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. 2019-07-19 Thesis (University of Nottingham only) NonPeerReviewed application/pdf en arr https://eprints.nottingham.ac.uk/56823/1/KONSTANTOULAKI_MRes%20Thesis_4296226.pdf Konstantoulaki, Katerina (2019) Role of NMNAT2 regulation in cortical primary neurons. MRes thesis, University of Nottingham. nmnat2 Neurons Degeneration Neuronal degeneration Wallerian degeneration Axons Axonal degeneration Neurodegeneration microRNA miRNA Cortical Cortical neurons n2a
spellingShingle nmnat2
Neurons
Degeneration
Neuronal degeneration
Wallerian degeneration
Axons
Axonal degeneration
Neurodegeneration
microRNA
miRNA
Cortical
Cortical neurons
n2a
Konstantoulaki, Katerina
Role of NMNAT2 regulation in cortical primary neurons
title Role of NMNAT2 regulation in cortical primary neurons
title_full Role of NMNAT2 regulation in cortical primary neurons
title_fullStr Role of NMNAT2 regulation in cortical primary neurons
title_full_unstemmed Role of NMNAT2 regulation in cortical primary neurons
title_short Role of NMNAT2 regulation in cortical primary neurons
title_sort role of nmnat2 regulation in cortical primary neurons
topic nmnat2
Neurons
Degeneration
Neuronal degeneration
Wallerian degeneration
Axons
Axonal degeneration
Neurodegeneration
microRNA
miRNA
Cortical
Cortical neurons
n2a
url https://eprints.nottingham.ac.uk/56823/