PMID- 16909021
OWN - NLM
STAT- MEDLINE
DCOM- 20060926
LR  - 20131121
IS  - 1660-2854 (Print)
IS  - 1660-2854 (Linking)
VI  - 2
IP  - 3-4
DP  - 2005
TI  - Enprofylline protects motor neurons from in vitro excitotoxic challenge.
PG  - 160-5
AB  - BACKGROUND: The death of motor neurons in amyotrophic lateral sclerosis (ALS) is 
      believed to result, in part, from unrestrained activation of glutamate receptors 
      (excitotoxicity). In some in vitro models, excitotoxic death only occurs if motor 
      neurons develop in the presence of the growth factor, brain-derived neurotrophic 
      factor (BDNF). OBJECTIVE: Since the increased vulnerability of motor neurons 
      evoked by BDNF is mediated by activation of TrkB, we sought to identify 
      pharmacological agents that can block this pathway. Adenosine receptors are known 
      to transactivate Trk receptors, leading us to examine the effects of manipulating 
      of adenosine receptor signaling on Trk signaling and excitotoxic sensitivity. 
      METHODS: Spinal cord cultures were treated with adenosine receptor agonists and 
      antagonists. The biochemical effects on Trk signaling and excitotoxic motor 
      neuron death were examined. RESULTS: We show here that adenosine A(2a) 
      antagonists can reduce activation of Trk receptors and are neuroprotective. 
      Conversely, activating adenosine A(2a) receptors in the absence of BDNF signaling 
      makes motor neurons vulnerable to excitotoxic challenge. CONCLUSION: Selective, 
      high-affinity adenosine A(2a) antagonists merit consideration as therapeutic 
      agents for the treatment of ALS.
FAU - Mojsilovic-Petrovic, Jelena
AU  - Mojsilovic-Petrovic J
AD  - Children's Hospital of Philadelphia, Joseph Stokes Jr. Research Institute, PA 
      19104, USA.
FAU - Arneja, Amrita
AU  - Arneja A
FAU - Kalb, Robert G
AU  - Kalb RG
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Switzerland
TA  - Neurodegener Dis
JT  - Neuro-degenerative diseases
JID - 101189034
RN  - 0 (Excitatory Amino Acid Agonists)
RN  - 0 (Excitatory Amino Acid Antagonists)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Receptors, Adenosine A2)
RN  - 0 (Xanthines)
RN  - DT7DT5E518 (enprofylline)
RN  - EC 2.7.10.1 (Receptor, trkB)
RN  - SIV03811UC (Kainic Acid)
SB  - IM
MH  - Animals
MH  - Animals, Newborn
MH  - Blotting, Western
MH  - Cells, Cultured
MH  - Excitatory Amino Acid Agonists/toxicity
MH  - Excitatory Amino Acid Antagonists/pharmacology
MH  - Kainic Acid/toxicity
MH  - Motor Neurons/*drug effects
MH  - Neuroprotective Agents/*pharmacology
MH  - Rats
MH  - Rats, Sprague-Dawley
MH  - Receptor, trkB/metabolism
MH  - Receptors, Adenosine A2/drug effects/metabolism
MH  - Xanthines/*pharmacology
EDAT- 2006/08/16 09:00
MHDA- 2006/09/27 09:00
CRDT- 2006/08/16 09:00
PHST- 2006/08/16 09:00 [pubmed]
PHST- 2006/09/27 09:00 [medline]
PHST- 2006/08/16 09:00 [entrez]
AID - 89621 [pii]
AID - 10.1159/000089621 [doi]
PST - ppublish
SO  - Neurodegener Dis. 2005;2(3-4):160-5. doi: 10.1159/000089621.