Final Activity Report Summary - NEUROPROTOLEIC (The role of oleic acid in the development and neuroprotection of the central nervous system)
Summary
Our previous work has shown that oleic acid is a neurotrophic factor that promotes neural differentiation. Oleic acid is taken up by neurons in which it induces neuronal differentiation by promoting axonal growth, neuronal clustering, and the expression of GAP-43 and MAP-3, markers of axonal or dendritic development, respectively. Moreover, during the postnatal period the increase in the concentrations of free oleic acid in the brain is accompanied by the expression of GAP-43 and MAP-2 concurrent with postnatal "secondary neurogenesis", a phenomenon observed in "non-precocious species" such as humans. In this work, we attempted to gain insight into the cellular and molecular mechanisms by which oleic acid promotes neuronal differentiation in order to understand the role of this oleic acid in brain development. Knowledge of these aspects may be of use in modulating the nutritional status of newborns in order to enhance their intellectual development. In addition, our results may help to understand the possible neuroprotector role of oleic acid in brain degeneration. If so, oleic acid may be used in the treatment of degenerative diseases such as Alzheimer's or Parkinson's.
Objectives
1. To attempt to elucidate the mechanism of action of oleic acid as a neutrophic factor. The role played by transcription factors of the NeuroD family, protein kinases, etc. The zonal distribution of oleic acid synthesis in the brain through localisation of SCD by in situ hybridisation.
2. To study the synergistic effect of oleic acid with neurotrophins and other neurotrophic factors. Differentials effects of NGF, BDNF, NT-3 and NT-4/5
3. To study the putative receptors of oleic acid in neurons and to search for agonists that can mimic the effects of oleic acid on neuronal differentiation.
4. To study the mechanism of oleic transport to the brain. The role played by serum albumin and its endocytosis. Manipulation of the transport mechanism in order to achieve therapeutic concentrations into the brain.
Achievements
1. Nex-1, a BHLH transcription factor belonging to the NeuroD family (NeuroD6), mediates the neurotrophic effect of oleic acid during postnatal development of the brain.
2. Megalin is the receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid.
Our previous work has shown that oleic acid is a neurotrophic factor that promotes neural differentiation. Oleic acid is taken up by neurons in which it induces neuronal differentiation by promoting axonal growth, neuronal clustering, and the expression of GAP-43 and MAP-3, markers of axonal or dendritic development, respectively. Moreover, during the postnatal period the increase in the concentrations of free oleic acid in the brain is accompanied by the expression of GAP-43 and MAP-2 concurrent with postnatal "secondary neurogenesis", a phenomenon observed in "non-precocious species" such as humans. In this work, we attempted to gain insight into the cellular and molecular mechanisms by which oleic acid promotes neuronal differentiation in order to understand the role of this oleic acid in brain development. Knowledge of these aspects may be of use in modulating the nutritional status of newborns in order to enhance their intellectual development. In addition, our results may help to understand the possible neuroprotector role of oleic acid in brain degeneration. If so, oleic acid may be used in the treatment of degenerative diseases such as Alzheimer's or Parkinson's.
Objectives
1. To attempt to elucidate the mechanism of action of oleic acid as a neutrophic factor. The role played by transcription factors of the NeuroD family, protein kinases, etc. The zonal distribution of oleic acid synthesis in the brain through localisation of SCD by in situ hybridisation.
2. To study the synergistic effect of oleic acid with neurotrophins and other neurotrophic factors. Differentials effects of NGF, BDNF, NT-3 and NT-4/5
3. To study the putative receptors of oleic acid in neurons and to search for agonists that can mimic the effects of oleic acid on neuronal differentiation.
4. To study the mechanism of oleic transport to the brain. The role played by serum albumin and its endocytosis. Manipulation of the transport mechanism in order to achieve therapeutic concentrations into the brain.
Achievements
1. Nex-1, a BHLH transcription factor belonging to the NeuroD family (NeuroD6), mediates the neurotrophic effect of oleic acid during postnatal development of the brain.
2. Megalin is the receptor for albumin in astrocytes and is required for the synthesis of the neurotrophic factor oleic acid.