1. Anti-Inflammatory Effect of IKK-Activated GSK-3β Inhibitory Peptide Prevented Nigrostriatal Neurodegeneration in the Rodent Model of Parkinson's Disease.
- Author
-
Lee, Seulah, Hong, Dong Geun, Yang, Seonguk, Kim, Jaehoon, Baek, Minwoo, Kim, Seoyeong, Thirumalai, Dinakaran, Chung, Hae Young, Chang, Seung-Cheol, and Lee, Jaewon
- Subjects
PARKINSON'S disease ,PEPTIDES ,GLYCOGEN synthase kinase ,NEURODEGENERATION ,SERINE/THREONINE kinases ,PROTEIN kinases ,NF-kappa B - Abstract
Parkinson's disease (PD) is a progressive movement disorder caused by nigrostriatal neurodegeneration. Since chronically activated neuroinflammation accelerates neurodegeneration in PD, we considered that modulating chronic neuroinflammatory response might provide a novel therapeutic approach. Glycogen synthase kinase 3 (GSK-3) is a multifunctional serine/threonine protein kinase with two isoforms, GSK-3α and GSK-3β, and GSK-3β plays crucial roles in inflammatory response, which include microglial migration and peripheral immune cell activation. GSK-3β inhibitory peptide (IAGIP) is specifically activated by activated inhibitory kappa B kinase (IKK), and its therapeutic effects have been demonstrated in a mouse model of colitis. Here, we investigated whether the anti-inflammatory effects of IAGIP prevent neurodegeneration in the rodent model of PD. IAGIP significantly reduced MPP
+ -induced astrocyte activation and inflammatory response in primary astrocytes without affecting the phosphorylations of ERK or JNK. In addition, IAGIP inhibited LPS-induced cell migration and p65 activation in BV-2 microglial cells. In vivo study using an MPTP-induced mouse model of PD revealed that intravenous IAGIP effectively prevented motor dysfunction and nigrostriatal neurodegeneration. Our findings suggest that IAGIP has a curative potential in PD models and could offer new therapeutic possibilities for targeting PD. [ABSTRACT FROM AUTHOR]- Published
- 2022
- Full Text
- View/download PDF