PMID- 23934644
OWN - NLM
STAT- MEDLINE
DCOM- 20141027
LR  - 20211021
IS  - 1559-1182 (Electronic)
IS  - 0893-7648 (Linking)
VI  - 49
IP  - 1
DP  - 2014 Feb
TI  - The proform of glia cell line-derived neurotrophic factor: a potentially 
      biologically active protein.
PG  - 234-50
LID - 10.1007/s12035-013-8515-6 [doi]
AB  - Growing evidences have revealed that the proforms of several neurotrophins 
      including nerve growth factor (NGF), brain-derived neurotrophic factor (BDNF), 
      and neurotrophin-3 (NT3), by binding to p75 neurotrophin receptor and sortilin, 
      could induce neuronal apoptosis and are implicated in the pathogenesis of various 
      neurodegenerative diseases. The glial cell line-derived neurotrophic factor 
      (GDNF), one of the most potent useful neurotrophic factors for the treatment of 
      Parkinson's disease (PD), is firstly synthesized as the proform (proGDNF) like 
      other neurotrophin NGF, BDNF, and NT3. However, little is known about proGDNF 
      expression and secretion under physiological as well as pathological states in 
      vivo or in vitro. In this study, we investigated the expression profile and 
      dynamic changes of proGDNF in brains of aging and PD animal models, with the 
      interesting finding that proGDNF was a predominant form of GDNF with molecular 
      weight of about 36 kDa by reducing and nonreducing immunoblots in adult brains 
      and was unregulated in the aging, lipopolysaccharide (LPS), and 
      1-methyl-4-phenyl- 1,2,3,6-tetrahydropyridine (MPTP) insult. We further provided 
      direct evidence that accompanied activation of primary astrocytes as well as C6 
      cell line induced by LPS stimulation, proGDNF was increasingly synthesized and 
      released as the uncleaved form in cell culture. Taken together, our results 
      strongly suggest that proGDNF may be a biologically active protein and has 
      specific effects on the cells close to its secreting site, and a potentially 
      important role of proGDNF signaling in the brains, in the glia-neuronal 
      interaction or in the pathogenesis of PD, should merit further investigation.
FAU - Sun, Xiao-Long
AU  - Sun XL
AD  - Institute of Neurosciences, Fourth Military Medical University, Xi'an, 710032, 
      People's Republic of China.
FAU - Chen, Bei-Yu
AU  - Chen BY
FAU - Duan, Li
AU  - Duan L
FAU - Xia, Yi
AU  - Xia Y
FAU - Luo, Zhuo-Jing
AU  - Luo ZJ
FAU - Wang, Jing-Jie
AU  - Wang JJ
FAU - Rao, Zhi-Ren
AU  - Rao ZR
FAU - Chen, Liang-Wei
AU  - Chen LW
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130810
PL  - United States
TA  - Mol Neurobiol
JT  - Molecular neurobiology
JID - 8900963
RN  - 0 (Gdnf protein, mouse)
RN  - 0 (Gdnf protein, rat)
RN  - 0 (Glial Cell Line-Derived Neurotrophic Factor)
RN  - 0 (Protein Precursors)
SB  - IM
MH  - Aging/genetics/*metabolism/pathology
MH  - Amino Acid Sequence
MH  - Animals
MH  - Brain/*metabolism/pathology
MH  - Columbidae
MH  - Disease Models, Animal
MH  - Glial Cell Line-Derived Neurotrophic Factor/*biosynthesis/genetics/metabolism
MH  - Humans
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - Parkinsonian Disorders/genetics/*metabolism/*pathology
MH  - Protein Precursors/*biosynthesis/genetics/metabolism
MH  - Rats
MH  - Rats, Sprague-Dawley
EDAT- 2013/08/13 06:00
MHDA- 2014/10/28 06:00
CRDT- 2013/08/13 06:00
PHST- 2013/05/07 00:00 [received]
PHST- 2013/07/10 00:00 [accepted]
PHST- 2013/08/13 06:00 [entrez]
PHST- 2013/08/13 06:00 [pubmed]
PHST- 2014/10/28 06:00 [medline]
AID - 10.1007/s12035-013-8515-6 [doi]
PST - ppublish
SO  - Mol Neurobiol. 2014 Feb;49(1):234-50. doi: 10.1007/s12035-013-8515-6. Epub 2013 
      Aug 10.