The main neuropathological features of Parkinson's disease are dopaminergic nigrostriatal neuron degeneration, and intraneuronal and intraneuritic proteinaceous inclusions named Lewy bodies and Lewy neurites, respectively, which mainly contain alpha-synuclein (alpha-syn, also known as SNCA). The neuronal phosphoprotein synapsin III (also known as SYN3), is a pivotal regulator of dopamine neuron synaptic function. Here, we show that alpha-syn interacts with and modulates synapsin III. The absence of alpha-syn causes a selective increase and redistribution of synapsin III, and changes the organization of synaptic vesicle pools in dopamine neurons. In alpha-syn-null mice, the alterations of synapsin III induce an increased locomotor response to the stimulation of synapsin-dependent dopamine overflow, despite this, these mice show decreased basal and depolarization-dependent striatal dopamine release. Of note, synapsin III seems to be involved in alpha-syn aggregation, which also coaxes its increase and redistribution. Furthermore, synapsin III accumulates in the caudate and putamen of individuals with Parkinson's disease. These findings support a reciprocal modulatory interaction of alpha-syn and synapsin III in the regulation of dopamine neuron synaptic function.

α-synuclein and synapsin III cooperatively regulate synaptic function in dopamine neurons

Zaltieri, Michela;Grigoletto, Jessica;Longhena, Francesca;Navarria, Laura;Favero, Gaia;Castrezzati, Stefania;Rezzani, Rita;Pizzi, Marina;Missale, Mariacristina;Spano, Pierfranco;Bellucci, Arianna
2015-01-01

Abstract

The main neuropathological features of Parkinson's disease are dopaminergic nigrostriatal neuron degeneration, and intraneuronal and intraneuritic proteinaceous inclusions named Lewy bodies and Lewy neurites, respectively, which mainly contain alpha-synuclein (alpha-syn, also known as SNCA). The neuronal phosphoprotein synapsin III (also known as SYN3), is a pivotal regulator of dopamine neuron synaptic function. Here, we show that alpha-syn interacts with and modulates synapsin III. The absence of alpha-syn causes a selective increase and redistribution of synapsin III, and changes the organization of synaptic vesicle pools in dopamine neurons. In alpha-syn-null mice, the alterations of synapsin III induce an increased locomotor response to the stimulation of synapsin-dependent dopamine overflow, despite this, these mice show decreased basal and depolarization-dependent striatal dopamine release. Of note, synapsin III seems to be involved in alpha-syn aggregation, which also coaxes its increase and redistribution. Furthermore, synapsin III accumulates in the caudate and putamen of individuals with Parkinson's disease. These findings support a reciprocal modulatory interaction of alpha-syn and synapsin III in the regulation of dopamine neuron synaptic function.
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/11379/461821
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