Toward a unified biological hypothesis for the BDNF Val66Met-associated memory deficits in humans: a model of impaired dendritic mRNA trafficking

Brain-derived neurotrophic factor (BDNF) represents a key molecule for the support of survival and differentiation of specific populations of neurons in the central nervous system. BDNF has also been involved in plasticity-related processes such as memory and learning. A common single nucleotide polymorphism (SNP) rs6265 has been identified on the coding sequence of human Brain derived neurotrophic factor located at 11p13. The SNP rs6265 is a single base mutation with an adenine instead of a guanine at position 196 (G196A) resulting in the aminoacidic substitution Val66Met. This polymorphism only exists in humans and has been associated with a plethora of effects ranging from molecular, cellular and brain structural modifications in association with deficits in social and cognitive functions. The data present in literature report complex and often conflicting pattern of results. In this review, in the attempt to provide a unifying model of the Val66Met effects, we will discuss the clinical evidence of the association between Val66Met and memory deficits, as well as the molecular mechanism involved which include both reduced transport of mRNA to the dendrites as well as reduced processing and secretion through the regulated secretory pathway.