Parkinson’s Disease (PD) is one the most common neurodegenerative movement disorder, it is characterized by degeneration of the dopaminergic nigrostriatal system and the presence of intraneuronal inclusions mainly composed by aggregates of alpha-synuclein, known as Lewy bodies (LB). Recently, we demonstrated that alpha-synuclein interacts and cooperates with the synaptic phosphoprotein synapsin III, a crucial regulator of striatal synaptic release. The specific aim of this study was to clarify whether synapsin III plays a role in the onset of alpha-synuclein-related synaptic damage in PD. To this purpose, we performed immunohistochemical and molecular biology studies on post-mortem caudate/putamen and substantia nigra samples from patients affected by PD and age-matched controls. Human cerebrospinal fluid (CSF) samples from subjects affected by different alpha-synucleinopathies were also analyzed. We found a significant accumulation of synapsin III in the caudate/putamen of patients affected by PD when compared to matched controls. Co-immunoprecipitation studies showed that synapsin III interaction with alpha-synuclein is detectable both in the brain and in the CSF of patients affected by alpha-synucleinopaties. Finally, we also demonstrated that synapsin III manipulation in vitro could be involved in alpha-synuclein aggregation, as its downregulation can prevent this phenomenon. Our findings suggest that synapsin III may play an important role in the onset synaptic dysfunction in PD. The existence of a cooperative pathological interaction between alpha-synuclein and synapsin III in the pathogenesis of PD deserves further investigation.
Synapsin III and Alpha-Synuclein cooperation in the onset of synaptic pathology in Parkinson’s Disease
Longhena F.;Zaltieri M;Faustini G.;Benfenati F.;Pizzi M.;Poliani P.;Borroni B.;Padovani A.;Missale C.;Spano P.;Bellucci A.
2017-01-01
Abstract
Parkinson’s Disease (PD) is one the most common neurodegenerative movement disorder, it is characterized by degeneration of the dopaminergic nigrostriatal system and the presence of intraneuronal inclusions mainly composed by aggregates of alpha-synuclein, known as Lewy bodies (LB). Recently, we demonstrated that alpha-synuclein interacts and cooperates with the synaptic phosphoprotein synapsin III, a crucial regulator of striatal synaptic release. The specific aim of this study was to clarify whether synapsin III plays a role in the onset of alpha-synuclein-related synaptic damage in PD. To this purpose, we performed immunohistochemical and molecular biology studies on post-mortem caudate/putamen and substantia nigra samples from patients affected by PD and age-matched controls. Human cerebrospinal fluid (CSF) samples from subjects affected by different alpha-synucleinopathies were also analyzed. We found a significant accumulation of synapsin III in the caudate/putamen of patients affected by PD when compared to matched controls. Co-immunoprecipitation studies showed that synapsin III interaction with alpha-synuclein is detectable both in the brain and in the CSF of patients affected by alpha-synucleinopaties. Finally, we also demonstrated that synapsin III manipulation in vitro could be involved in alpha-synuclein aggregation, as its downregulation can prevent this phenomenon. Our findings suggest that synapsin III may play an important role in the onset synaptic dysfunction in PD. The existence of a cooperative pathological interaction between alpha-synuclein and synapsin III in the pathogenesis of PD deserves further investigation.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
