Shen Ting, You Yuyi, Joseph Chitra, Mirzaei Mehdi, Klistorner Alexander, Graham Stuart L, Gupta Vivek
1Faculty of Medicine and Health Sciences, Macquarie University, Australia.
2Save Sight Institute, Sydney University, Sydney, Australia.
Aging Dis. 2018 Jun 1;9(3):523-536. doi: 10.14336/AD.2017.0717. eCollection 2018 Jun.
Brain-derived neurotrophic factor (BDNF) has a unique role in the neuronal development, differentiation, and survival in the developing and adult nervous system. A common single-nucleotide polymorphism in the pro-region of the human BDNF gene, resulting in a valine to methionine substitution (Val66Met), has been associated with the susceptibility, incidence, and clinical features of several neurodegenerative disorders. Much research has been dedicated to evaluating the effects of polymorphism in the past decade, and functional effects of this genetic variation. A better understanding of how this naturally occurring polymorphism associates with or influences physiology, anatomy, and cognition in both healthy and diseased adults in neurodegenerative conditions will help understand neurochemical mechanisms and definable clinical outcomes in humans. Here we review the role and relevance of the BDNF Val66Met polymorphism in neurodegenerative diseases, with particular emphasis on glaucoma, multiple sclerosis (MS), Alzheimer's disease (AD) and Parkinson's disease (PD). Several controversies and unresolved issues, including small effect sizes, possible ethnicity, gender, and age effects of the BDNF Val66Met are also discussed with respect to future research.
脑源性神经营养因子（BDNF）在发育中和成年神经系统的神经元发育、分化及存活过程中发挥着独特作用。人类BDNF基因前区域存在一种常见的单核苷酸多态性，导致缬氨酸被甲硫氨酸取代（Val66Met），这与多种神经退行性疾病的易感性、发病率及临床特征相关。在过去十年里，大量研究致力于评估该多态性的影响以及这种基因变异的功能效应。更好地理解这种自然发生的多态性在神经退行性疾病中如何与健康和患病成年人的生理、解剖及认知相关联或产生影响，将有助于理解人类的神经化学机制及明确的临床结果。在此，我们综述BDNF Val66Met多态性在神经退行性疾病中的作用及相关性，尤其着重于青光眼、多发性硬化症（MS）、阿尔茨海默病（AD）和帕金森病（PD）。同时，还针对未来研究讨论了一些争议和未解决的问题，包括BDNF Val66Met效应量小、可能存在的种族、性别及年龄效应等。
