The key neuropathological hallmarks of Parkinson’s disease (PD) are nigro-striatal dopamine neuron loss and intraneuronal Lewy Bodies (LB), proteinaceous inclusions mainly composed by α-synuclein. Recently, we demonstrated a reciprocal modulatory interaction between α-synuclein and synapsin III, a synaptic vesicles-associated phosphoprotein that plays a crucial role in dopamine (DA) release and synaptic vesicle arrangement. The aim of this study was to investigate whether synapsin III alterations may be present in association with α-synuclein pathology in the brain of patients affected by PD (Human brain samples were kindly provided by the UK Parkinson’s disease Brain Bank) and Dementia with LB (DLB). By immunohistochemistry, we observed a marked accumulation of synapsin III in the caudate/putamen of patients affected by PD when compared to age matched controls. In addition, many LB-like structures in the substantia nigra of PD patients as well as in the hippocampus of a patient affected by DLB were found to be immunoreactive for synapsin III, that by confocal fluorescence microscopy resulted to be accumulated in the core of LB. By co-immunoprecipitation, we found that synapsin III directly interacted with α-synuclein in the human brain. Finally, western blot analysis showed significant alterations of synapsin III levels in the caudate/putamen and substantia nigra of PD patients. Of note, similar alterations were observed in a human α-synuclein transgenic mouse model of PD. Altogether, our data support a critical involvement of synapsin III in PD pathophysiology.
Synapsin III Alteration in Parkinson's disease
Longhena F.;Zaltieri M.;Grigoletto J.;Favero G.;Castrezzati S.;Pizzi M.;Rezzani R.;Benfenati F.;Poliani P. L.;Missale C.;Spano P.;Bellucci A
2015-01-01
Abstract
The key neuropathological hallmarks of Parkinson’s disease (PD) are nigro-striatal dopamine neuron loss and intraneuronal Lewy Bodies (LB), proteinaceous inclusions mainly composed by α-synuclein. Recently, we demonstrated a reciprocal modulatory interaction between α-synuclein and synapsin III, a synaptic vesicles-associated phosphoprotein that plays a crucial role in dopamine (DA) release and synaptic vesicle arrangement. The aim of this study was to investigate whether synapsin III alterations may be present in association with α-synuclein pathology in the brain of patients affected by PD (Human brain samples were kindly provided by the UK Parkinson’s disease Brain Bank) and Dementia with LB (DLB). By immunohistochemistry, we observed a marked accumulation of synapsin III in the caudate/putamen of patients affected by PD when compared to age matched controls. In addition, many LB-like structures in the substantia nigra of PD patients as well as in the hippocampus of a patient affected by DLB were found to be immunoreactive for synapsin III, that by confocal fluorescence microscopy resulted to be accumulated in the core of LB. By co-immunoprecipitation, we found that synapsin III directly interacted with α-synuclein in the human brain. Finally, western blot analysis showed significant alterations of synapsin III levels in the caudate/putamen and substantia nigra of PD patients. Of note, similar alterations were observed in a human α-synuclein transgenic mouse model of PD. Altogether, our data support a critical involvement of synapsin III in PD pathophysiology.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
