Neurochemical Research

, Volume 44, Issue 4, pp 751–762 | Cite as

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


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.


Parkinson’s disease MPTP Tyrosine hydroxylase Dopamine PPARα 



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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© 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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