Anti-Inflammatory Effect of IKK-Activated GSK-3β Inhibitory Peptide Prevented Nigrostriatal Neurodegeneration in the Rodent Model of Parkinson’s Disease |
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| Authors: | Seulah Lee Dong Geun Hong Seonguk Yang Jaehoon Kim Minwoo Baek Seoyeong Kim Dinakaran Thirumalai Hae Young Chung Seung-Cheol Chang Jaewon Lee |
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| Affiliation: | 1.Department of Pharmacy, College of Pharmacy, Pusan National University, Busan 46241, Korea; (S.L.); (D.G.H.); (S.Y.); (J.K.); (M.B.); (S.K.); (H.Y.C.);2.Research Institute for Drug Development, Pusan National University, Busan 46241, Korea;3.Department of Cogno-Mechatronics Engineering, College of Nanoscience and Nanotechnology, Pusan National University, Busan 46241, Korea; (D.T.); (S.-C.C.) |
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| 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. |
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| Keywords: | Parkinson’ s disease inhibitory κ B kinase-activated GSK-3β inhibitory peptide 1-methyl-4-phenyl-1 2 3 6-tetrahydropyridine neuroinflammation anti-inflammation |
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