In Parkinson’s disease (PD) accumulation of alpha-synuclein at striatal synapses, the neuronal sites of dopamine release, is believed to trigger cell degeneration. We have found that Synapsin III (Syn III), a synaptic protein that negatively regulates dopamine release, is involved in alpha-synuclein aggregation. The aim of this project is to test whether Syn III is a pivotal mediator of the alpha-synuclein-aggregation-related dopaminergic damage.
We will induce alpha-synuclein overexpression in pre-clinical models bred without Syn III and in normal pre-clinical models. We will perform biochemical and molecular biology studies to investigate whether the absence of Syn III can hamper alpha-synuclein aggregation and the onset of dopaminergic dysfunction and cell degeneration.
Relevance to Diagnosis/Treatment of Parkinson’s Disease:
Alpha-synuclein is a crucial protein involved in the pathogenesis of PD, however it is not yet clear what factors are involved in initiating its aggregation and how that clumping induces dysfunction and dopamine neuron loss. The results of our investigation can provide new insights into PD pathophysiology and a new direction for therapeutic intervention for PD.
By finding whether the absence of Syn III can prevent alpha-synuclein aggregation and the onset of dopamine neuron degeneration, this study can pave the way for the development of novel drug treatments to slow or stop PD.