Objective: This study deals to investigate and explore the anti-apoptotic and molecular mechanisms of CGA in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) induced Parkinsonian mice model.

Background: The debilitating neurodegenerative disorder, Parkinson’s disease (PD) occurs due to the loss of dopaminergic (DA) neurons via programmed cell death or apoptosis. Oxidative and nitrative stress, inflammation, mitochondrial dysfunction and aberration in proteolysis are the major factors accountable for the pathogenesis of PD. All these factors further attribute to a complex cascade of interrelated events that ultimately triggers apoptosis. A naturally occurring polyphenolic compound, Chlorogenic acid (CGA) is found in variety of fruits and vegetables and exhibits different biological properties such as anti-apoptotic, anti-inflammatory, neurotropic and free radical scavenging activities.

Method: To accomplish this study, thirty two adult male mice were randomly selected and divided into four groups (n = 8 each): Control; MPTP; MPTP+CGA; and CGA. Our results have stated that CGA treatment has alleviated the motor deficits in MPTP intoxicated mice.

Results: Administration of CGA to MPTP intoxicated mice has protected the DA neurons against MPTP insult via its anti-apoptotic activity by reversing the dysregulated expression of Bcl-2, Bax, and Caspase-3. The elevated activity of pAkt after CGA supplementation reveals about the mechanistic action of CGA which has concomitantly prevented the apoptosis of the DA neurons. Besides, TH immunoreactive DA neurons were also found to be significantly increased in the substantia nigra pars compacta area upon CGA supplementation. Real time PCR analysis has shown the reduced gene expression of pro-inflammatory markers (IL-1β, IL-2 and IL-6) due to CGA treatment after MPTP intoxication.

Conclusion: In conclusion, CGA protected the DA neurons probably through its anti-apoptotic effect and may act as an effective agent for the treatment of PD.

References: 1. Singh SS, Rai SN, Birla H, Zahra W, Kumar G, Gedda MR, Tiwari N, Patnaik R, Singh RK and Singh SP (2018) Effect of Chlorogenic Acid Supplementation in MPTP-Intoxicated Mouse. Front. Pharmacol. 9:757. doi: 10.3389/fphar.2018.00757 2. Poewe, W. S. K., Tanner, C. M., Halliday, G. M., Halliday, G. M., Brundin, P., Volkmann, J., et al. (2017). Parkinson disease. Nat. Rev. Dis. Primers 23:17013. doi: 10.1038/nrdp.2017.13

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MDS Abstracts - https://www.mdsabstracts.org/abstract/chlorogenic-acid-attenuates-the-mptp-induced-apoptosis-in-parkinsons-disease-mouse-model-through-pakt-signaling-pathway/