Neurotrophic factors NGF and FGF-2 alter levels of huntingtin (IT15) in striatal neuronal cell cultures.
A mutation of the human IT15 gene is responsible for Huntington's disease (HD) and the causative factor in the major neuronal loss observed in the striatum. The growth factors basic fibroblast growth factor (FGF-2), nerve growth factor (NGF), and brain-derived neurotrophic factor (BDNF) improve survival and promote differentiation of striatal neurons, as well as exert a neuroprotective effect when such neurons are challenged with metabolic toxins or excitatory amino acids. Using Western blotting and striatal cell cultures, we found that FGF-2 increased the level of huntingtin in a dose-dependent fashion, whereas NGF decreased huntingtin expression. The neurotrophic factor-specific, dose-dependent effect on striatal levels of huntingtin may be relevant to understanding the normal role of IT15 and developing new therapies against the disease provoking mutated IT15.
Haque
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NS
Department of Neurology, Massachusetts General Hospital, Belmont 02178, USA.
Isacson
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O
D000818:Animals; D015153:Blotting, Western; D019208:Brain-Derived Neurotrophic Factor / Q000494:pharmacology; D002478:Cells, Cultured; D003342:Corpus Striatum / Q000187:drug effects / Q000378:metabolism*; D016222:Fibroblast Growth Factor 2 / Q000494:pharmacology*; D015870:Gene Expression; D000071058:Huntingtin Protein; D020932:Nerve Growth Factor / Q000494:pharmacology*; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley
D019208:Brain-Derived Neurotrophic Factor; C499524:Htt protein, rat; D000071058:Huntingtin Protein; D009419:Nerve Tissue Proteins; D009687:Nuclear Proteins; D011506:Proteins; D016222:Fibroblast Growth Factor 2; D020932:Nerve Growth Factor