Journal
NEURODEGENERATIVE DISEASES
Volume 15, Issue 4, Pages 207-218Publisher
KARGER
DOI: 10.1159/000375447
Keywords
Huntington's disease; Mutant huntingtin; BDNF; TrkB receptors; Caspase-3; Apoptosis
Categories
Funding
- 'Fundacao para a Ciencia e a Tecnologia' (FCT), Portugal [PTDC/SAU-FCF/108056/2008]
- POPH - 'Programa Operacional Potencial Humano'
- QREN - 'Quadro de Referencia Estrategico Nacional'
- Fundo Social Europeu da Uniao Europeia
- COMPETE - Programa Operacional Factores de Competitividade
- Faculty of Medicine, University of Coimbra [PEI-HDCR01]
- CNC - FCT, FEDER, and COMPETE
- FCT [SFRH/BD/30147/2006, SFRH/BD/41285/2007, SFRH/BD/86655/2012]
Ask authors/readers for more resources
Background: Several cellular mechanisms have been proposed to explain the pathogenesis of Huntington's disease (HD), including the lack of striatal brain-derived neurotrophic factor (BDNF). Thus, by preferentially binding to troponnyosin receptor kinase B (TrkB) receptor, BDNF is an important neurotrophin implicated in striatal neuronal survival. Objective: To study the influence of BDNF and TrkB receptors in intracellular signaling pathways and caspase-3 activation in HD striatal cells. Methods: HD mutant knockin and wild-type striatal cells were transduced with preproBDNF or full-length TrkB receptors to analyze BDNF processing, AKT and extracellular signal-regulated kinase (ERK) activation and the activity of caspase-3 in the absence or presence of staurosporine (STS). Results: HD mutant cells transduced with preproBDNF-mCherry (mCh) expressed similar levels of pro- and mature BDNF compared to WT cells, but HD cells released lower levels of pro- and mature BDNF. Despite this, BDNF-mCh overexpression rescued decreased AKT phosphorylation and reduced the caspase-3 activation observed in HD cells. Activated ERK was also enhanced in HD BDNF-mCh/TrkB-eGFP receptor co-cultures. Of relevance, overexpression of TrkB-eGFP in HD cells decreased caspase-3 activation, and stimulation of TrkB-eGFP-transduced mutant cells with recombinant human BDNF reduced both basal and STS-induced caspase-3 activation. Conclusion: The results highlight the importance of BDNF-induced TrkB receptor signaling in rescuing HD-mediated apoptotic features in striatal cells. (C) 2015 S. Karger AG, Basel
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available