PMID- 12829403
OWN - NLM
STAT- PubMed-not-MEDLINE
LR  - 20230320
IS  - 1476-3524 (Electronic)
IS  - 1029-8428 (Linking)
VI  - 4
IP  - 3
DP  - 2002 May
TI  - Gangliosides prevent excitotoxicity through activation of TrkB receptor.
PG  - 225-34
AB  - Gangliosides protect cerebellar granule cells from excitotoxicity; however, their 
      mechanism of action remains to be fully characterized. GM1 ganglioside has been 
      shown to activate Trk, the tyrosine kinase receptor implicated in the 
      neuroprotective properties of the neurotrophins. In these studies, we used 
      primary cultures of cerebellar granule cells to determine whether gangliosides 
      exert neuroprotective effect via the activation of Trk receptors. We first 
      examined the relative potency of the neurotrophins, brain derived neurotrophic 
      factor (BDNF), neurotrophin-3 and nerve growth factor to prevent 
      glutamate-mediated apoptosis. BDNF was the only neurotrophin that elicited a 
      complete neuronal protection against glutamate. GM1 and its semisynthetic 
      compound LIGA20 also prevented glutamate toxicity, however, LIGA20 was more 
      potent than GM1. Both LIGA20 and BDNF blocked glutamate-mediated activation of 
      caspase-3 and consequently apoptosis; however, the anticaspase-3 activity was 
      seen only when these compounds were added to the cultures several hours before 
      glutamate, suggesting that LIGA20 and BDNF share an identical molecular 
      mechanism. To test this hypothesis, we compared the ability of LIGA20 and BDNF to 
      activate TrkB. Both compounds elicited a similar time-dependent increase in Trk 
      tyrosine phosphorylation. Moreover, the neuroprotective effect of BDNF and LIGA20 
      was abolished in neurons exposed to the Trk tyrosine kinase inhibitor k252a, 
      demonstrating a relationship between neuroprotection and activation of Trk 
      receptors. Our data suggest that by activating the Trk neurotrophin receptors, 
      gangliosides may be used as neuroprotective agents.
FAU - Bachis, Alessia
AU  - Bachis A
AD  - Department of Neuroscience, Georgetown University, Medical School, Research 
      Building, 3970 Reservoir Rd NW, Washington, D.C. 20007, USA. 
      moccheti@georgetown.edu
FAU - Rabin, Stuart J
AU  - Rabin SJ
FAU - Del Fiacco, Marina
AU  - Del Fiacco M
FAU - Mocchetti, Italo
AU  - Mocchetti I
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Neurotox Res
JT  - Neurotoxicity research
JID - 100929017
EDAT- 2003/06/28 05:00
MHDA- 2003/06/28 05:01
CRDT- 2003/06/28 05:00
PHST- 2003/06/28 05:00 [pubmed]
PHST- 2003/06/28 05:01 [medline]
PHST- 2003/06/28 05:00 [entrez]
AID - 10.1080/10298420290015836 [doi]
PST - ppublish
SO  - Neurotox Res. 2002 May;4(3):225-34. doi: 10.1080/10298420290015836.