Abstract
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.
Highlights
Neurotrophins are a family of growth factors crucial for the regulation of neuronal maintenance, differentiation, and survival
A naturally occurring polymorphism in the human brain-derived neurotrophic factor (BDNF) gene leading to an amino-acid residue substitution from valine (Val) to methionine (Met) at position 66 within the pro-region of BDNF, results in a functional single-nucleotide polymorphism (SNP) that possibly results in altered BDNF activity-dependent secretion [1]
We discuss the potential involvement of BDNF polymorphism in several neurodegenerative disorders, and conclude that the evidence is mixed in terms of implicating the SNP in several common diseases
Summary
The BDNF gene is localized on chromosome 11 band p13 [4] and comprises 11 exons and 9 functional promoters [21]. PCR genotyping method of amplified refractory mutation system was reported to be cost-effective, efficient, and as reliable as PCR-RFLP for detecting BDNF polymorphisms [25]. The understanding of BDNF function in humans has greatly benefited from the identification of a SNP in the BDNF gene that causes a valine (Val) to methionine (Met) substitution at codon 66 (Val66Met, c.196G>A, dbSNP: rs6265). In this Met variant form of BDNF carriers, that is, BDNF Val/Met heterozygotes and Met/Met. homozygotes, the pro-domain structure of the gene is altered. The Val66Met polymorphism is not known to occur naturally in other vertebrate species except the human so far [31]
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