PMID- 17188890
OWN - NLM
STAT- MEDLINE
DCOM- 20070417
LR  - 20181201
IS  - 1044-7431 (Print)
IS  - 1095-9327 (Electronic)
IS  - 1044-7431 (Linking)
VI  - 34
IP  - 2
DP  - 2007 Feb
TI  - Pro-NGF secreted by astrocytes promotes motor neuron cell death.
PG  - 271-9
AB  - It is well established that motor neurons depend for their survival on many 
      trophic factors. In this study, we show that the precursor form of NGF (pro-NGF) 
      can induce the death of motor neurons via engagement of the p75 neurotrophin 
      receptor. The pro-apoptotic activity was dependent upon the presence of sortilin, 
      a p75 co-receptor expressed on motor neurons. One potential source of pro-NGF is 
      reactive astrocytes, which up-regulate the levels of pro-NGF in response to 
      peroxynitrite, an oxidant and producer of free radicals. Indeed, motor neuron 
      viability was sensitive to conditioned media from cultured astrocytes treated 
      with peroxynitrite and this effect could be reversed using a specific antibody 
      against the pro-domain of pro-NGF. These results are consistent with a role for 
      activated astrocytes and pro-NGF in the induction of motor neuron death and 
      suggest a possible therapeutic target for the treatment of motor neuron disease.
FAU - Domeniconi, Marco
AU  - Domeniconi M
AD  - Molecular Neurobiology Program, Skirball Institute of Biomolecular Medicine, 
      Department of Cell Biology, New York University School of Medicine, 540 First 
      Avenue, New York, NY 10016, USA.
FAU - Hempstead, Barbara L
AU  - Hempstead BL
FAU - Chao, Moses V
AU  - Chao MV
LA  - eng
GR  - HD023315/HD/NICHD NIH HHS/United States
GR  - P01 HD023315/HD/NICHD NIH HHS/United States
GR  - NS21072/NS/NINDS NIH HHS/United States
GR  - R01 NS021072/NS/NINDS NIH HHS/United States
GR  - P01 HD023315-200002/HD/NICHD NIH HHS/United States
GR  - R01 NS021072-22/NS/NINDS NIH HHS/United States
GR  - R01 AG025970/AG/NIA NIH HHS/United States
GR  - R56 NS021072/NS/NINDS NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20061226
PL  - United States
TA  - Mol Cell Neurosci
JT  - Molecular and cellular neurosciences
JID - 9100095
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Culture Media, Conditioned)
RN  - 0 (Homeodomain Proteins)
RN  - 0 (LIM-Homeodomain Proteins)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (Nerve Growth Factors)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Protein Precursors)
RN  - 0 (Transcription Factors)
RN  - 0 (insulin gene enhancer binding protein Isl-1)
RN  - 0 (pro-nerve growth factor, rat)
RN  - 14691-52-2 (Peroxynitrous Acid)
RN  - Z020Y8WIJ4 (sortilin)
SB  - IM
MH  - Adaptor Proteins, Vesicular Transport
MH  - Analysis of Variance
MH  - Animals
MH  - Animals, Newborn
MH  - Astrocytes/*chemistry
MH  - Cell Death/drug effects
MH  - Cells, Cultured
MH  - Culture Media, Conditioned/pharmacology
MH  - Embryo, Mammalian
MH  - Gene Expression/drug effects/physiology
MH  - Homeodomain Proteins/metabolism
MH  - LIM-Homeodomain Proteins
MH  - Membrane Glycoproteins/metabolism
MH  - Motor Neurons/*drug effects
MH  - Nerve Growth Factors/*pharmacology
MH  - Nerve Tissue Proteins/metabolism
MH  - Peroxynitrous Acid/pharmacology
MH  - Protein Precursors/*pharmacology
MH  - Rats
MH  - Spinal Cord/cytology
MH  - Transcription Factors
PMC - PMC2570110
MID - NIHMS18062
EDAT- 2006/12/26 09:00
MHDA- 2007/04/18 09:00
PMCR- 2008/10/20
CRDT- 2006/12/26 09:00
PHST- 2006/08/18 00:00 [received]
PHST- 2006/10/23 00:00 [revised]
PHST- 2006/11/10 00:00 [accepted]
PHST- 2006/12/26 09:00 [pubmed]
PHST- 2007/04/18 09:00 [medline]
PHST- 2006/12/26 09:00 [entrez]
PHST- 2008/10/20 00:00 [pmc-release]
AID - S1044-7431(06)00257-0 [pii]
AID - 10.1016/j.mcn.2006.11.005 [doi]
PST - ppublish
SO  - Mol Cell Neurosci. 2007 Feb;34(2):271-9. doi: 10.1016/j.mcn.2006.11.005. Epub 
      2006 Dec 26.