We found a match
Your institution may have access to this item. Find your institution then sign in to continue.
- Title
PEP-1-GLRX1 Reduces Dopaminergic Neuronal Cell Loss by Modulating MAPK and Apoptosis Signaling in Parkinson's Disease.
- Authors
Choi, Yeon Joo; Kim, Dae Won; Shin, Min Jea; Yeo, Hyeon Ji; Yeo, Eun Ji; Lee, Lee Re; Song, Yejin; Kim, Duk-Soo; Han, Kyu Hyung; Park, Jinseu; Lee, Keun Wook; Park, Jong Kook; Eum, Won Sik; Choi, Soo Young
- Abstract
Parkinson's disease (PD) is characterized mainly by the loss of dopaminergic neurons in the substantia nigra (SN) mediated via oxidative stress. Although glutaredoxin-1 (GLRX1) is known as one of the antioxidants involved in cell survival, the effects of GLRX1 on PD are still unclear. In this study, we investigated whether cell-permeable PEP-1-GLRX1 inhibits dopaminergic neuronal cell death induced by 1-methyl-4-phenylpyridinium (MPP+) and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). We showed that PEP-1-GLRX1 protects cell death and DNA damage in MPP+-exposed SH-SY5Y cells via the inhibition of MAPK, Akt, and NF-κB activation and the regulation of apoptosis-related protein expression. Furthermore, we found that PEP-1-GLRX1 was delivered to the SN via the blood–brain barrier (BBB) and reduced the loss of dopaminergic neurons in the MPTP-induced PD model. These results indicate that PEP-1-GLRX1 markedly inhibited the loss of dopaminergic neurons in MPP+- and MPTP-induced cytotoxicity, suggesting that this fusion protein may represent a novel therapeutic agent against PD.
- Subjects
PARKINSON'S disease; DOPAMINERGIC neurons; MITOGEN-activated protein kinases; BLOOD-brain barrier; CHIMERIC proteins; CELL survival; APOPTOSIS
- Publication
Molecules, 2021, Vol 26, Issue 11, p3329
- ISSN
1420-3049
- Publication type
Article
- DOI
10.3390/molecules26113329