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KMID : 0624620230560020126
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BMB Reports
2023 Volume.56 No. 2 p.126 ~ p.131
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The couple of netrin-1/α-Synuclein regulates the survival of dopaminergic neurons via α-Synuclein disaggregation
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Kang Eun-Ji
Jang Seung-Min
Lee Ye-Ji
Jeong Ye-Ji
Kim You-Jin
Kang Seong-Su
Ahn Eun-Hee
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Abstract
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The abnormal accumulation and aggregation of the misfolded α-synuclein protein is the neuropathological hallmark of all α-synucleinopathies, including Parkinson’s disease. The secreted proteins known as netrins (netrin-1, netrin-3, and netrin-4) are related to laminin and have a role in the molecular pathway for axon guidance and cell survival. Interestingly, only netrin-1 is significantly expressed in the substantia nigra (SN) of healthy adult brains and its expression inversely correlates with that of α-synuclein, which prompted us to look into the role of α-synuclein and netrin-1 molecular interaction in the future of dopaminergic neurons. Here, we showed that netrin-1 and α-synuclein directly interacted in pre-formed fibrils (PFFs) generation test, real time binding assay, and co-immunoprecipitation with neurotoxin treated cell lysates. Netrin-1 deficiency appeared to activate the dopaminergic neuronal cell death signal pathway via α-synuclein aggregation and hyperphosphorylation of α-synuclein S129. Taken together, netrin-1 can be a promising therapeutic molecule in Parkinson’s disease.
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KEYWORD
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α-synuclein, Dopaminergic neuron, Molecule-molecule interaction, Netrin-1, Parkinson’s disease
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