Neuroprotective Effects Of Fingolimod In Mouse Models Of Parkinson'S Disease

Department

neurobiology

Document Type

Article

Abstract

Parkinson's disease (PD) is characterized by a progressive loss of dopaminergic neurons with limited treatment options. Emerging evidence shows that FTY720 protects against neural injury via modulation of the sphingosine-1-phosphate 1 receptor (S1PR1). However, it remains unclear whether FTY720 could influence neurodegeneration in PD.Therefore, the present studywas designed to determine the impact of fingolimod (FTY720), a sphingosine-1-phosphate receptor (S1PR) agonist, on 2 mouse models of PD. We found that FTY720 significantly reduced the deficit of motor function, diminished the loss of tyrosine hydroxylase-positive neurons in the substantia nigra, and attenuated the decrease of striatal dopamine and metabolite levels in mice receiving 6-hydroxydopamine (6-OHDA) or rotenone to simulate PD. An S1PR1-selective antagonist, W146, blocked the neuroprotective effects of FTY720.Of note, FTY720 retained the phosphorylation of ERK, together with a decreased expressionof cleaved caspase-3 inmice treatedwith6-OHDAor rotenone. In vitro studies revealedthat FTY720 also attenuated 6-OHDA- or rotenone-induced toxicity in SH-SY5Y cells. These findings suggest the potential of S1PR modulation as a treatment for PD.-Zhao, P., Yang, X., Yang, L., Li, M., Wood, K., Liu, Q., Zhu, X. Neuroprotective effects of fingolimod in mouse models of Parkinson's disease. FASEB J. 31, 172-179 (2017). www.fasebj.org.

Publication Date

1-1-2017

Publication Title

FASEB Journal

ISSN

08926638

Volume

31

Issue

1

First Page

172

Last Page

179

Digital Object Identifier (DOI)

10.1096/fj.201600751R

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