원문정보
초록
영어
α-Synuclein has been proposed to play a key pathogen in Parkinson's disease (PD). Especially, the abnormal accumulation and aggregation of the misfolded α-Synuclein protein is the neuropathological hallmark of all α-Synucleinopathies, including Parkinson's disease. Netrins (netrin-1, netrin-3, and netrin-4) are secreted proteins, which are laminin-related and involved in axon guidance function and cell survival molecular pathway. Remarkably, only netrin-1 is highly expressed in healthy adult substantia nigra brain region and inversely correlates with the expression of α-Synuclein, which led us to investigate the impact of the molecular interaction between α-Synuclein and netrin-1 in dopaminergic neuron fate. Here we show that netrin-1 and α-Synuclein directly interact in pre-formed fibrils (PFFs) generation test and real time binding assay. Strikingly, we observed that the level of netrin-1 was significantly decreased in SNCA Tg mouse brain with dopaminergic cell death, which matched the analysis result from human PD patients database. Our finding suggest that netrin-1 deprivation triggers dopaminergic neuronal cell death with α-Synuclein aggregation during aging process and netrin-1 can be the promising therapeutic or diagnostic molecule in α-Synucleinopathies.