| First Author | Guo C | Year | 2024 |
| Journal | Sci Rep | Volume | 14 |
| Issue | 1 | Pages | 8581 |
| PubMed ID | 38615036 | Mgi Jnum | J:348472 |
| Mgi Id | MGI:7622896 | Doi | 10.1038/s41598-024-59090-8 |
| Citation | Guo C, et al. (2024) Plasminogen degrades alpha-synuclein, Tau and TDP-43 and decreases dopaminergic neurodegeneration in mouse models of Parkinson's disease. Sci Rep 14(1):8581 |
| abstractText | Parkinson's disease (PD) is the second most frequently diagnosed neurodegenerative disease, and it is characterized by the intracellular and extracellular accumulation of alpha-synuclein (alpha-syn) and Tau, which are major components of cytosolic protein inclusions called Lewy bodies, in the brain. Currently, there is a lack of effective methods that preventing PD progression. It has been suggested that the plasminogen activation system, which is a major extracellular proteolysis system, is involved in PD pathogenesis. We investigated the functional roles of plasminogen in vitro in an okadaic acid-induced Tau hyperphosphorylation NSC34 cell model, ex vivo using brains from normal controls and methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated mice, and in vivo in a widely used MPTP-induced PD mouse model and an alpha-syn overexpression mouse model. The in vitro, ex vivo and in vivo results showed that the administered plasminogen crossed the bloodbrain barrier (BBB), entered cells, and migrated to the nucleus, increased plasmin activity intracellularly, bound to alpha-syn through lysine binding sites, significantly promoted alpha-syn, Tau and TDP-43 clearance intracellularly and even intranuclearly in the brain, decreased dopaminergic neurodegeneration and increased the tyrosine hydroxylase levels in the substantia nigra and striatum, and improved motor function in PD mouse models. These findings indicate that plasminogen plays a wide range of pivotal protective roles in PD and therefore may be a promising drug candidate for PD treatment. |
