Abstract
Prof. Dr. Peter Riederer, the former Head of the Neurochemistry Department of the Psychiatry and Psychotherapy Clinic at the University of Würzburg (Germany), has been one of the pioneers of research into oxidative stress in Parkinson's and Alzheimer’s disease (AD). This review will outline how his scientific contribution to the field has opened a new direction for AD treatment beyond “plaques and tangles”. In the 1990s, Prof. Riederer was one of the first scientists who proposed oxidative stress and neuroinflammation as one of the major contributors to Alzheimer’s disease, despite the overwhelming support for the “amyloid-only” hypothesis at the time, which postulated that the sole and only cause of AD is β-amyloid. His group also highlighted the role of advanced glycation end products, sugar and dicarbonyl-derived protein modifications, which crosslink proteins into insoluble aggregates and potent pro-inflammatory activators of microglia. For the treatment of chronic neuroinflammation, he and his group suggested that the most appropriate drug class would be cytokine-suppressive anti-inflammatory drugs (CSAIDs) which have a broader anti-inflammatory action range than conventional non-steroidal anti-inflammatory drugs. One of the most potent CSAIDs is curcumin, but it suffers from a variety of pharmacokinetic disadvantages including low bioavailability, which might have tainted many human clinical trials. Although a variety of oral formulations with increased bioavailability have been developed, curcumin’s absorption after oral delivery is too low to reach therapeutic concentrations in the micromolar range in the systemic circulation and the brain. This review will conclude with evidence that rectally applied suppositories might be the best alternatives to oral medications, as this route will be able to evade first-pass metabolism in the liver and achieve high concentrations of curcumin in plasma and tissues, including the brain.
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Acknowledgements
Some of the experimental work was supported by a Ph.D. scholarship from the Western Sydney University (to M.V), and an ARC Linkage grant with Integria Healthcare (Grant number: LP160101594, to X. Z, G.M). X.Z. is supported by the Research Support Program Fellowship, Western Sydney University. No funding was received to assist with the preparation of this manuscript.
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All authors contributed to the study’s conception and design. Material preparation, experiments, data collection, and analysis were performed by MV and XZ. The first draft of the manuscript was written by GWM (who was mentored by Prof. Riederer) and developed the idea of a historical review idea, and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.
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Dedicated to Prof. Riederer’s 80th birthday.
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Zhou, X., Venigalla, M., Raju, R. et al. Pharmacological considerations for treating neuroinflammation with curcumin in Alzheimer’s disease. J Neural Transm 129, 755–771 (2022). https://doi.org/10.1007/s00702-022-02480-x
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DOI: https://doi.org/10.1007/s00702-022-02480-x