PMID- 24859383
OWN - NLM
STAT- MEDLINE
DCOM- 20160314
LR  - 20220316
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 51
IP  - 2
DP  - 2015 Apr
TI  - Induction of GDNF and BDNF by hRheb(S16H) transduction of SNpc neurons: 
      neuroprotective mechanisms of hRheb(S16H) in a model of Parkinson's disease.
PG  - 487-99
LID - 10.1007/s12035-014-8729-2 [doi]
AB  - The transduction of dopaminergic (DA) neurons with human ras homolog enriched in 
      brain, which has a S16H mutation [hRheb(S16H)] protects the nigrostriatal DA 
      projection in the 6-hydroxydopamine (6-OHDA)-treated animal model of Parkinson's 
      disease (PD). However, it is still unclear whether the expression of active hRheb 
      induces the production of neurotrophic factors such as glial cell line-derived 
      neurotrophic factor (GDNF) and brain-derived neurotrophic factor (BDNF), which 
      are involved in neuroprotection, in mature neurons. Here, we show that 
      transduction of nigral DA neurons with hRheb(S16H) significantly increases the 
      levels of phospho-cyclic adenosine monophosphate (cAMP) response element-binding 
      protein (p-CREB), GDNF, and BDNF in neurons, which are attenuated by rapamycin, a 
      specific inhibitor of mammalian target of rapamycin complex 1 (mTORC1). Moreover, 
      treatment with specific neutralizing antibodies for GDNF and BDNF reduced the 
      protective effects of hRheb(S16H) against 1-methyl-4-phenylpyridinium 
      (MPP(+))-induced neurotoxicity. These results show that activation of 
      hRheb/mTORC1 signaling pathway could impart to DA neurons the important ability 
      to continuously produce GDNF and BDNF as therapeutic agents against PD.
FAU - Nam, Jin Han
AU  - Nam JH
AD  - Department of Neuroscience, Neurodegeneration Control Research Center, School of 
      Medicine, Kyung Hee University, Seoul, 130-701, Korea.
FAU - Leem, Eunju
AU  - Leem E
FAU - Jeon, Min-Tae
AU  - Jeon MT
FAU - Jeong, Kyoung Hoon
AU  - Jeong KH
FAU - Park, Jeen-Woo
AU  - Park JW
FAU - Jung, Un Ju
AU  - Jung UJ
FAU - Kholodilov, Nikolai
AU  - Kholodilov N
FAU - Burke, Robert E
AU  - Burke RE
FAU - Jin, Byung Kwan
AU  - Jin BK
FAU - Kim, Sang Ryong
AU  - Kim SR
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20140525
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Neuropeptides)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (RHEB protein, human)
RN  - 0 (Ras Homolog Enriched in Brain Protein)
RN  - EC 3.6.5.2 (Monomeric GTP-Binding Proteins)
SB  - IM
MH  - Animals
MH  - Brain-Derived Neurotrophic Factor/*biosynthesis
MH  - *Disease Models, Animal
MH  - Glial Cell Line-Derived Neurotrophic Factor/*biosynthesis
MH  - Humans
MH  - Monomeric GTP-Binding Proteins/*pharmacology/therapeutic use
MH  - Neurons/drug effects/*metabolism
MH  - Neuropeptides/*pharmacology/therapeutic use
MH  - Neuroprotective Agents/pharmacology/therapeutic use
MH  - Parkinson Disease/*metabolism/prevention & control
MH  - Ras Homolog Enriched in Brain Protein
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Substantia Nigra/drug effects/metabolism
EDAT- 2014/05/27 06:00
MHDA- 2016/03/15 06:00
CRDT- 2014/05/27 06:00
PHST- 2014/02/20 00:00 [received]
PHST- 2014/04/29 00:00 [accepted]
PHST- 2014/05/27 06:00 [entrez]
PHST- 2014/05/27 06:00 [pubmed]
PHST- 2016/03/15 06:00 [medline]
AID - 10.1007/s12035-014-8729-2 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2015 Apr;51(2):487-99. doi: 10.1007/s12035-014-8729-2. Epub 2014 
      May 25.