The BDNF Val66Met polymorphism (rs6265) enhances dopamine neuron graft efficacy and side-effect liability in rs6265 knock-in rats.
The BDNF Val66Met polymorphism (rs6265) enhances dopamine neuron graft efficacy and side-effect liability in rs6265 knock-in rats.
Neurobiol Dis. 2020 Nov 11;:105175
Authors: Mercado NM, Stancati JA, Sortwell CE, Mueller RL, Boezwinkle SA, Duffy MF, Fischer DL, Sandoval IM, Manfredsson FP, Collier TJ, Steece-Collier K
Abstract
Prevalent in approximately 20% of the worldwide human population, the rs6265 (also called 'Val66Met') single nucleotide polymorphism (SNP) in the gene for brain-derived neurotrophic factor (BDNF) is a common genetic variant that can alter therapeutic responses in individuals with Parkinson's disease (PD). Possession of the variant M, et al.lele results in decreased activity-dependent release of BDNF. Given the resurgent worldwide interest in neural transplantation for PD and the biological relevance of BDNF, the current studies examined the effects of the rs6265 SNP on therapeutic efficacy and side-effect development following primary dopamine (DA) neuron transplantation. Considering the significant reduction in BDNF release associated with rs6265, we hypothesized that rs6265-mediated dysfunctional BDNF signaling contributes to the limited clinical benefit observed in a subpopulation of PD patients despite robust survival of grafted DA neurons, and further, that this mutation contributes to the development of aberrant graft-induced dyskinesias (GID). To this end, we generated a CRISPR knock-in rat model of the ...
Source: Neurobiology of Disease - Category: Neurology Authors: Mercado NM, Stancati JA, Sortwell CE, Mueller RL, Boezwinkle SA, Duffy MF, Fischer DL, Sandoval IM, Manfredsson FP, Collier TJ, Steece-Collier K Tags: Neurobiol Dis Source Type: research