a-Synuclein is a neuronal protein particularly abundant in forebrain structures in rodents and humans, localized mainly in pre-synaptic terminals and in the neighborhood of synaptic vesicles, and suggested to be involved in trafficking of synaptic vesicles. a-Synuclein is a major protein component of Lewy bodies (LB), the histopathological hallmark of Parkinson's disease (PD) and dementia with LBs. Two mutations in the a-synuclein gene have been found to cause familial forms of PD characterized by extensive loss of nigral dopaminergic neurons and loss of dopamine in the striatum. Studies of transgenic rodents and Drosophila models strongly implicate a-synuclein in the degeneration of dopaminergic neurons, but its molecular mechanisms remain to be clarified. In order to increase our knowledge on the regulation of a-synuclein in dopaminergic neurons we defined an experimental model of human dopaminergic neuroblastoma cell induced to differentiation by di-butyryl-cyclic AMP (db-cAMP). The assessment of SH-SY5Y cell differentiation was evaluated following the formation of neuritis and the expression of neuronal markers. We present a protocol of differentiation based on the exposure of SH-SY5Y to db-cAMP. This protocol yields a population of neuronal differentiated cells evaluated by analysing the expression of neuronal markers bIII tubulin and GAP43. An increase of a-synuclein was associated with the expression of the neuronal markers detected during the differentiation of human dopaminergic SH-SY5Y cell. This model offers a convenient system to explore the effect of different agents on the mechanisms involving a-synuclein modifications and dopaminergic cell degeneration detected in brains of patients affected by Lewy body-relate pathology.
Dozza B., Zaccheo D., Strocchi P. (2004). REGULATION OF a-SYNUCLEIN DURING HUMAN NEUROBLASTOMA CELL DIFFERENTIATION. s.l : s.n.
REGULATION OF a-SYNUCLEIN DURING HUMAN NEUROBLASTOMA CELL DIFFERENTIATION
DOZZA, BARBARA;STROCCHI, PAOLA
2004
Abstract
a-Synuclein is a neuronal protein particularly abundant in forebrain structures in rodents and humans, localized mainly in pre-synaptic terminals and in the neighborhood of synaptic vesicles, and suggested to be involved in trafficking of synaptic vesicles. a-Synuclein is a major protein component of Lewy bodies (LB), the histopathological hallmark of Parkinson's disease (PD) and dementia with LBs. Two mutations in the a-synuclein gene have been found to cause familial forms of PD characterized by extensive loss of nigral dopaminergic neurons and loss of dopamine in the striatum. Studies of transgenic rodents and Drosophila models strongly implicate a-synuclein in the degeneration of dopaminergic neurons, but its molecular mechanisms remain to be clarified. In order to increase our knowledge on the regulation of a-synuclein in dopaminergic neurons we defined an experimental model of human dopaminergic neuroblastoma cell induced to differentiation by di-butyryl-cyclic AMP (db-cAMP). The assessment of SH-SY5Y cell differentiation was evaluated following the formation of neuritis and the expression of neuronal markers. We present a protocol of differentiation based on the exposure of SH-SY5Y to db-cAMP. This protocol yields a population of neuronal differentiated cells evaluated by analysing the expression of neuronal markers bIII tubulin and GAP43. An increase of a-synuclein was associated with the expression of the neuronal markers detected during the differentiation of human dopaminergic SH-SY5Y cell. This model offers a convenient system to explore the effect of different agents on the mechanisms involving a-synuclein modifications and dopaminergic cell degeneration detected in brains of patients affected by Lewy body-relate pathology.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
