Molecular mechanisms underlying BDNF functions in .. (Neurotrophins-ARMS)
Molecular mechanisms underlying BDNF functions in the brain: role of ARMS protein
Start date: Jan 1, 2008,
End date: Dec 31, 2011
Neurotrophins are growth factors including NGF, BDNF, NT-3 and NT-4, which function in cell survival, differentiation, apoptosis, axonal and dendritic growth, and plasticity in the nervous system. Additionally, BDNF has been implicated in human brain pathologies, such as depression, Alzheimer, Huntington, Parkinson, etc. Neurotrophins bind to two different sets of receptors, Trk and p75 receptors, to mediate their functions. Trk activation leads to its phosphorylation in tyrosine and the phosphorylated residues work as docking sites for different adaptor molecules, such as Shc, PLC-γ, FRS-2, SH2B and APS. Recently, a new molecule, ARMS/Kidins220, has been described in association with Trk receptors. ARMS is tyrosine phosphorylated in primary hippocampal and cortical neurons in response to neurotrophins, and is involved in the sustained MAPK mediated by neurotrophins. My work hypothesis is that ARMS/Kidins220 may be an important molecule in neurotrophin functions. For this reason, we propose the study of ARMS/Kidins220 in the differentiation, dendritic branching and neuronal synaptic plasticity mediated by BDNF. The study will be carried out using biochemical and cellular techniques together with molecular biology and genetic approaches. The detailed study of ARMS/Kidins220 will provide a better understanding of the neurotrophin functions as well as the molecular mechanisms that regulate neurotrophin actions and its potential role in nervous system pathologies.
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