Parkinson's disease (PD) is characterized by the formation of Lewy body in dopaminergic neurons in the substantia nigra pars compacta (SNpc).
Alpha-synuclein (α-syn) is a major component of Lewy body. Autophagy eliminates damaged organelles and abnormal aggregated
proteins.
Thioredoxin-1 (Trx-1) is a redox regulating
protein and plays roles in protecting dopaminergic neurons against neurotoxicity induced by
1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (
MPTP). However, the relationship between Trx-1 and α-syn in PD is still unknown. In the present study, the
movement disorder and dopaminergic neurotoxicity in
MPTP-treated mice were improved by Trx-1 overexpression and were aggravated by Trx-1 knockdown in the SNpc in mice. The expression of α-syn was increased in the SNpc of
MPTP-treated mice, which was inhibited by Trx-1 overexpression and was exacerbated in Trx-1 knockdown mice. Autophagosomes was increased under electron microscope after
MPTP treatment, which were recovered in Trx-1 overexpressing mice and were further increased in Trx-1 knockdown in the SNpc in mice. The expressions of
phosphatase and
tensin homolog deleted on chromosome ten (
PTEN)-induced putative kinase 1 (PINK1), Parkin, LC3 II and p62 were increased by
MPTP, which were blocked in Trx-1 overexpressing mice and were further increased in Trx-1 knockdown mice.
Cathepsin D was decreased by
MPTP, which was restored in Trx-1 overexpressing mice and was further decreased in Trx-1 knockdown mice. The mRFP-GFP-LC3 green fluorescent dots were increased by
1-methyl-4-phenylpyridinium (MPP+) and further increased in Trx-1
siRNA transfected PC12 cells, while mRFP-GFP-LC3 red fluorescent dots were increased in Trx-1 overexpressing cells. These results indicate that Trx-1 may eliminate α-syn in PD mice through potentiating autophagy-lysosome pathway.