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Cinnamic Acid Protects the Nigrostriatum in a Mouse Model of Parkinson’s Disease via Peroxisome Proliferator-Activated Receptorα

  • Tim Prorok
  • Malabendu Jana
  • Dhruv Patel
  • Kalipada PahanEmail author
Original Paper
  • 76 Downloads

Abstract

Parkinson’s disease (PD) is the second most common devastating human neurodegenerative disorder and despite intense investigation, no effective therapy is available for PD. Cinnamic acid, a naturally occurring aromatic fatty acid of low toxicity, is a precursor for the synthesis of a huge number of plant substances. This study highlights the neuroprotective effect of cinnamic acid in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. Oral administration of cinnamic acid protected tyrosine hydroxylase (TH)-positive dopaminergic neurons in the substantia nigra pars compacta (SNpc) and TH fibers in the striatum of MPTP-insulted mice. Accordingly, oral cinnamic acid also normalized striatal neurotransmitters and improved locomotor activities in MPTP-intoxicated mice. While investigating mechanisms, we found that cinnamic acid induced the activation of peroxisome proliferator-activated receptor α (PPARα), but not PPARβ, in primary mouse astrocytes. Cinnamic acid mediated protection of the nigrostriatal system and locomotor activities in WT and PPARβ (–/–), but not PPARα (–/–) mice from MPTP intoxication suggests that cinnamic acid requires the involvement of PPARα in protecting dopaminergic neurons in this model of PD. This study delineates a new function of cinnamic acid in protecting dopaminergic neurons via PPARα that could be beneficial for PD.

Keywords

Parkinson’s disease MPTP Tyrosine hydroxylase Dopamine PPARα 

Notes

Acknowledgements

This study was supported by a merit award from the Department of Veteran Affairs (1I01BX003033) and Grants (NS83054 and AG050431) from National Institutes of Health.

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  1. 1.Division of Research and DevelopmentJesse Brown Veterans Affairs Medical CenterChicagoUSA
  2. 2.Department of Neurological SciencesRush University Medical CenterChicagoUSA

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