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

Neurochem Res. 2019 Apr;44(4):751-762. doi: 10.1007/s11064-018-02705-0. Epub 2019 Jan 5.


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: Dopamine; MPTP; PPARα; Parkinson’s disease; Tyrosine hydroxylase.

MeSH terms

  • Animals
  • Cinnamates / pharmacology
  • Cinnamates / therapeutic use*
  • Corpus Striatum / drug effects
  • Corpus Striatum / metabolism*
  • Corpus Striatum / pathology
  • Disease Models, Animal
  • MPTP Poisoning / metabolism*
  • MPTP Poisoning / pathology
  • MPTP Poisoning / prevention & control
  • Mice
  • Mice, Inbred C57BL
  • Mice, Knockout
  • Neuroprotective Agents / pharmacology
  • Neuroprotective Agents / therapeutic use*
  • PPAR alpha / agonists
  • PPAR alpha / deficiency*
  • PPAR alpha / metabolism
  • Parkinsonian Disorders / metabolism
  • Parkinsonian Disorders / pathology
  • Parkinsonian Disorders / prevention & control
  • Substantia Nigra / drug effects
  • Substantia Nigra / metabolism*
  • Substantia Nigra / pathology


  • Cinnamates
  • Neuroprotective Agents
  • PPAR alpha
  • cinnamic acid