PMID- 25896770
OWN - NLM
STAT- MEDLINE
DCOM- 20160422
LR  - 20180816
IS  - 1660-2862 (Electronic)
IS  - 1660-2854 (Linking)
VI  - 15
IP  - 4
DP  - 2015
TI  - Overexpression of BDNF and Full-Length TrkB Receptor Ameliorate Striatal Neural 
      Survival in Huntington's Disease.
PG  - 207-18
LID - 10.1159/000375447 [doi]
AB  - 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 
      tropomyosin 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.
CI  - (c) 2015 S. Karger AG, Basel.
FAU - Silva, Ana
AU  - Silva A
AD  - CNC - Center for Neuroscience and Cell Biology, University of Coimbra, Coimbra, 
      Portugal.
FAU - Naia, Luana
AU  - Naia L
FAU - Dominguez, Alejandro
AU  - Dominguez A
FAU - Ribeiro, Marcio
AU  - Ribeiro M
FAU - Rodrigues, Joana
AU  - Rodrigues J
FAU - Vieira, Otilia V
AU  - Vieira OV
FAU - Lessmann, Volkmar
AU  - Lessmann V
FAU - Rego, Ana Cristina
AU  - Rego AC
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20150421
PL  - Switzerland
TA  - Neurodegener Dis
JT  - Neuro-degenerative diseases
JID - 101189034
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (HTT protein, human)
RN  - 0 (Huntingtin Protein)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Recombinant Proteins)
RN  - 7171WSG8A2 (BDNF protein, human)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - EC 2.7.10.1 (tropomyosin-related kinase-B, human)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 3.4.22.- (Caspase 3)
SB  - IM
EIN - Neurodegener Dis. 2015;15(4):258. PMID: 26227205
MH  - *Apoptosis
MH  - Brain-Derived Neurotrophic Factor/*metabolism
MH  - Caspase 3/metabolism
MH  - Cell Line
MH  - Corpus Striatum/*metabolism
MH  - Humans
MH  - Huntingtin Protein
MH  - Huntington Disease/*metabolism
MH  - MAP Kinase Signaling System
MH  - Membrane Glycoproteins/*metabolism
MH  - Nerve Tissue Proteins/metabolism
MH  - Neurons/*metabolism
MH  - Protein-Tyrosine Kinases/*metabolism
MH  - Proto-Oncogene Proteins c-akt/metabolism
MH  - Receptor, trkB
MH  - Recombinant Proteins/metabolism
MH  - Signal Transduction
EDAT- 2015/04/22 06:00
MHDA- 2016/04/23 06:00
CRDT- 2015/04/22 06:00
PHST- 2014/08/05 00:00 [received]
PHST- 2015/01/21 00:00 [accepted]
PHST- 2015/04/22 06:00 [entrez]
PHST- 2015/04/22 06:00 [pubmed]
PHST- 2016/04/23 06:00 [medline]
AID - 000375447 [pii]
AID - 10.1159/000375447 [doi]
PST - ppublish
SO  - Neurodegener Dis. 2015;15(4):207-18. doi: 10.1159/000375447. Epub 2015 Apr 21.