The couple of netrin-1/メ-Synuclein regulates the survival of dopaminergic neurons via メ-Synuclein disaggregation |
Eun Ji Kang 1 (Graduate student), Seung Min Jang 1 (Undergraduate student), Ye Ji Lee 1 (Graduate student), Ye Ji Jeong 1 (Undergraduate student), You Jin Kim1 (Undergraduate student), Seong Su Kang 2 (Professor), Eun Hee Ahn 1,* (Professor) |
1Department of Physiology, Hallym University College of Medicine, 2Department of Pathology and Laboratory Medicine, Emory University College of Medicine |
Abstract
The abnormal accumulation and aggregation of the misfolded メ-Synuclein protein is the neuropathological hallmark of all メ-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 メ-Synuclein, which led us to investigate the impact of the molecular interaction between メ-Synuclein and netrin-1 in dopaminergic neuron fate. Here we show that netrin-1 and メ-Synuclein directly interact in pre-formed fibrils (PFFs) generation test, real time binding assay, and Co-Immunoprecipitation with neurotoxin treated cell lysates. Our finding suggest that netrin-1 deprivation triggers dopaminergic neuronal cell death signal pathway with メ-Synuclein aggregation and hyperphosphorylates メ-Synuclein S129. Taken together, netrin-1 can be the promising therapeutic molecule in Parkinson’s disease.
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Abstract, Accepted Manuscript(in press) [Submitted on January 12, 2023, Accepted on February 4, 2023] |
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