Tat-aldose reductase prevents dopaminergic neuronal cell death by inhibiting oxidative stress and MAPK activation

Abstract

Aldose reductase (AR) is known to detoxify aldehydes and prevent oxidative stress. Although AR exerts antioxidant effects, the role of AR in Parkinson's disease (PD) remains unclear. The objective of the present study was to investigate the protective effects of AR protein against 1-methyl-4-phenylpyridinium (MPP+)-induced SH-SY5Y cell death and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced PD in a mouse model using the cell permeable Tat-AR fusion protein. The results revealed that when Tat-AR protein was transduced into SH-SY5Y cells, it markedly protected the cells against MPP+-induced death and DNA fragmentation. It also reduced the activation of mitogen-activated protein kinase (MAPKs) and regulated the expression levels of Bcl-2, Bax and caspase-3. Immunohistochemical analysis revealed that when Tat-AR protein was transduced into the substantia nigra (SN) of mice with PD, it markedly inhibited dopaminergic neuronal cell death. Therefore, Tat-AR may be useful as a therapeutic protein for PD.