Neuroprotection in Parkinson's Disease: A Systematic Review of the Preclinical Data

H. Douna1, §, B.M. Bavelaar1, §, H. Pellikaan2, B. Olivier1, T. Pieters*, 1, 3
1 Utrecht Institute for Pharmaceutical Sciences (UIPS), Utrecht University, The Netherlands
2 Next Step Pharma, Utrecht, The Netherlands
3 VU Medical Centre, Amsterdam, The Netherlands

© 2012 Douna et al;

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the the Department of Pharmacoepidemiology and Clinical Pharmacology, Faculty of Science, Utrecht University, Postbox 800 82, 3508 TB Utrecht, The Netherlands; Tel: +31302537324; E-mail:
§ Both authors contributed equally.


Aim: This study aimed to systematically review the preclinical data of neuroprotective agents for Parkinson’s disease (PD) to support the translation of these compounds.

Methods: The study consisted of two phases. In phase I, Pubmed and Scopus were systematically searched for neuroprotective agents for PD. In phase II, a systematic search was conducted for each substance identified in phase I. Articles were included if they used MPTP, 6-OHDA, rotenone or paraquat injury models.

Results: Phase I led to the identification of 168 putative neuroprotective agents. Eventually ten compounds were included: melatonin, estrogen, nicotine, caffeine, riluzole, curcumin, coenzyme Q10, aspirin, EGCG and resveratrol. Phase II revealed 113 experimental studies and three reviews.

Conclusion: This study clearly depicts the preclinical data of ten promising neuroprotective agents. While some of these compounds have already been tested in clinical use, none of them was studied in an appropriately designed trial to determine a neuroprotective effect. In expectation of qualitatively improved neuroprotection trials, the data from this study provide a firm foundation for future research.

Keywords: Aspirin, caffeine, coenzyme Q10, curcumin, EGCG, estrogen, melatonin, neuroprotection, neuroprotective agents, nicotine, Parkinson's disease, resveratrol, riluzole..