Resveratrol regulates phosphorylation of specific cytoskeletal proteins in LRRK2 R1441G Parkinson’s disease model mice

Abstract

Parkinson’s disease (PD) is a common chronic neurodegenerative disorder by progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta. Leucine-rich repeat kinase 2 (LRRK2) is the most common causative gene of autosomaldominant inherited PD. The LRRK2 protein contains multi-domains, including a GTPase and kinase domains. In this study, we checked for difference in phosphorylation level of various proteins between normal mice and LRRK2 R1441G transgenic mice brains. In LRRK2 R1441G mice, phosphorylation level of a-tubulin decreased whereas the amount of phospho-tau increased. Tubulin and tau are cytoskeletal proteins that play important roles in neuronal cell morphology. Therefore, we used resveratrol (RSV), which has neuroprotective function, to see its effect on primary culture cells from LRRK2 R1441G transgenic mice in vitro and change it brings to the transgenic mice in vivo. In vitro, treatment of resveratrol increased neurite lengths of hippocampus (HC) primary culture cells from postnatal 1 day LRRK2 R1441G transgenic mice. In vivo, RSV administration improved motor ability and decreased phospho-tau protein level. These results indicate that RSV regulates phosphorylation of specific cytoskeletal proteins which is related with dysfunctional cellular transport and abnormal neurite outgrowth in PD pathology.