Synapsin III alterations in Parkinson's disease

Objectives: The main neuropathological hallmarks of Parkinson's disease
(PD) are loss of nigro-striatal dopamine neurons and intraneuronal Lewy
Bodies (LB), proteinaceous inclusions mainly composed by a-synuclein.
Recently, we found that a-synuclein interacts and cooperates with a specific
member of the synapsin phosphoprotein family: synapsin III, in the
regulation of dopaminergic neuron function. The aim of this study was to
investigate whether synapsin III alterations may be related to a-synuclein
pathology in PD. We thus investigated the occurrence of alterations of
synapsin III expression and distribution in “the brain of patients affected
by PD and DLB (Human brain samples were kindly provided by the UK
Parkinson's disease Brain Bank).
Methods: We used molecular biology and immunohistochemical techniques
as well as the “in situ” proximity ligation assay (PLA) to investigate
the expression levels and the distribution of synapsin III in the PD brain.
Results: By immunohistochemistry, we showed 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 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 and “in situ”
PLA we found that synapsin III directly interacted with a-synuclein and
that these two proteins were co-redistributed in mice and human brains.
Finally, western blot analysis showed significant alterations of synapsin III
levels that correlated with alteration of a-synuclein in the caudate/putamen
and substantia nigra of PD patients.
Conclusions: Altogether, our data support a critical involvement of synapsin
III in PD pathophysiology