BACKGROUND. The main neuropathological hallmarks of Parkinson’s Disease (PD) are the loss of nigro-striatal dopamine (DA) neurons and the presence of intraneuronal inclusions mainly composed by alpha-synuclein known as Lewy Bodies (LB). Recently, we demonstrated that synapsin III, a specific member of the synapsin family, seems to be implicated in alpha-synuclein aggregation (Zaltieri et al., 2015). Of note, synapsin III functions as a negative modulator of striatal dopamine release (Kile et al., 2010). Although synapsin III alterations have been found to be related to the onset of neuropsychiatric disorders and multiple sclerosis (Cesca et al., 2010), studies describing whether this protein is altered in the PD brain were missing. AIM: The specific aim of this study was to clarify the role of synapsin III in the onset of synaptic damage related to alpha-synuclein pathology in PD. METHODS. To probe the involvement of synapsin III in alpha-synuclein aggregation, the distribution of synapsin III was studied by immunohystochemistry in the nigrostriatal system of mice transgenic for the human-C-terminally-truncated form -synuclein of 120 aa in length (SYN120 tg) as well as in post-mortem caudate/putamen and substantia nigra of PD patients and age-matched controls. We also performed preliminary studies on human cerebrospinal fluid (CSF) from patients affected by alpha-synucleinopathies to immunoprecipitate alpha-synuclein and study the possible interaction with synapsin III. RESULTS. We found marked changes in synapsin III distribution and levels in the nigrostriatal system of SYN120 tg mice as well as in the caudate/putamen of PD patients when compared to age-matched controls. In contrast, synapsin Ia/b distribution was not altered. Co-immunoprecipitation studies showed that synapsin III is associated with alpha-synuclein both in the brain and in the CSF. CONCLUSIONS.Our findings suggest that synapsin III participates to alpha-synuclein-pathology in PD.
Involvement of Synapsin III in the onset of Alpha-synuclein 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.
2016-01-01
Abstract
BACKGROUND. The main neuropathological hallmarks of Parkinson’s Disease (PD) are the loss of nigro-striatal dopamine (DA) neurons and the presence of intraneuronal inclusions mainly composed by alpha-synuclein known as Lewy Bodies (LB). Recently, we demonstrated that synapsin III, a specific member of the synapsin family, seems to be implicated in alpha-synuclein aggregation (Zaltieri et al., 2015). Of note, synapsin III functions as a negative modulator of striatal dopamine release (Kile et al., 2010). Although synapsin III alterations have been found to be related to the onset of neuropsychiatric disorders and multiple sclerosis (Cesca et al., 2010), studies describing whether this protein is altered in the PD brain were missing. AIM: The specific aim of this study was to clarify the role of synapsin III in the onset of synaptic damage related to alpha-synuclein pathology in PD. METHODS. To probe the involvement of synapsin III in alpha-synuclein aggregation, the distribution of synapsin III was studied by immunohystochemistry in the nigrostriatal system of mice transgenic for the human-C-terminally-truncated form -synuclein of 120 aa in length (SYN120 tg) as well as in post-mortem caudate/putamen and substantia nigra of PD patients and age-matched controls. We also performed preliminary studies on human cerebrospinal fluid (CSF) from patients affected by alpha-synucleinopathies to immunoprecipitate alpha-synuclein and study the possible interaction with synapsin III. RESULTS. We found marked changes in synapsin III distribution and levels in the nigrostriatal system of SYN120 tg mice as well as in the caudate/putamen of PD patients when compared to age-matched controls. In contrast, synapsin Ia/b distribution was not altered. Co-immunoprecipitation studies showed that synapsin III is associated with alpha-synuclein both in the brain and in the CSF. CONCLUSIONS.Our findings suggest that synapsin III participates to alpha-synuclein-pathology in PD.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
