Promotion of neuronal survival by GM1 ganglioside. Phenomenology and mechanism of action.
The purpose of this article is to review recent findings regarding the mechanisms by which GM1 may mimic or potentiate certain actions of neurotrophic factors, including promotion of neuronal survival. It is proposed that the neuroprotective activity of GM1 is due, at least in part, to its ability to favor the dimerization of neurotrophic factor tyrosine kinases and thereby mimicking the action of their corresponding ligands. This may manifest both in the absence of ligand (thereby triggering a subset of neurotrophic-factor responses such as prevention of apoptosis) and in the presence of ligand (thereby potentiating responses to neurotrophic factors).
Ferrari
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G
Fidia Research laboratories, Abano Terme, Italy. fidiaspa@protec.it
Greene
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LA
D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001665:Binding Sites; D002470:Cell Survival / Q000187:drug effects*; D019281:Dimerization; D005677:G(M1) Ganglioside / Q000378:metabolism / Q000494:pharmacology*; D006801:Humans; D008956:Models, Chemical; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000502:physiology; D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D020794:Receptor Protein-Tyrosine Kinases / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D020917:Receptor, trkA; D017475:Receptors, Nerve Growth Factor / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*
D018696:Neuroprotective Agents; D011518:Proto-Oncogene Proteins; D017475:Receptors, Nerve Growth Factor; D005677:G(M1) Ganglioside; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA