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Brain-Derived Neurotrophic Factor (BDNF) gene: interaction between Val66Met polymorphism and neurodegenerative diseases

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posted on 2022-11-22, 00:10 authored by Ting ShenTing Shen

Brain-derived neurotrophic factor (BDNF) plays an essential role in regulating the neuronal growth, differentiation and survival in the central nervous system (CNS). The dysregulation or deprivation of BDNF has been implicated in increased susceptibility to various neurodegenerative diseases. The functional single nucleotide polymorphism (SNP) that results in a valine-to-methionine substitution at codon 66 (Val66Met) in the pro region of BDNF gene has been reported to affect the intracellular processing and activity-dependent secretion of BDNF. In this thesis, I have investigated the association between BDNF Val66Met polymorphism and several neurodegenerative disorders, including open-angle glaucoma (OAG), neuromyelitis optica spectrum disorders (NMOSD) and multiple sclerosis (MS). The differential structural and functional patterns of optic nerve damage were also compared between two similar diseases of NMOSD and MS. The results demonstrated that the carriage of BDNF Met allele has a protective effect against nerve fibre loss and is associated with a reduced rate of long-term OAG progression in a gender-specific way. In NMOSD and MS, however, the BDNF Val66Met showed negative effects where the Met carriers exhibited more severe optic nerve damage caused by acute optic neuritis (ON) attacks. The opposite effects may suggest the involvement of other regulators or different interactions BDNF Met alleles may have with acute optic nerve impairment in inflammation and progressive glaucomatous optic neuropathy. Based on these observations, my studies indicate that BDNF Val66Met carriage may be useful prognostic markers that have differential disease-specific effects.


Table of Contents

Chapter 1: Literature review – Chapter 2: Materials and methods – Chapter 3: Sex-specific effect of BDNF Val66Met genotypes on the progression of open-angle glaucoma – Chapter 4: Differing structural and functional patterns of optic nerve damage in multiple sclerosis and neuromyelitis optica spectrum disorder – Chapter 5: Association between BDNF Val66Met polymorphism and optic neuritis damage in neuromyelitis optica spectrum disorder – Chapter 6: The Val66Met polymorphism of BDNF is associated with greater optic neuritis damage in multiple sclerosis – Chapter 7: Conclusion and future directions -- References

Awarding Institution

Macquarie University

Degree Type

Thesis PhD


Thesis (PhD), Department of Clinical Medicine, Faculty of Medicine, Health and Human Sciences, Macquarie University

Department, Centre or School

Department of Clinical Medicine

Year of Award


Principal Supervisor

Stuart L. Graham

Additional Supervisor 1

Vivek K. Gupta

Additional Supervisor 2

Yuyi You


Copyright: The Author Copyright disclaimer:




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