Abstract
Essential trace metals like zinc (Zn), iron (Fe), and copper (Cu) play an important physiological role in the metabolomics and healthy functioning of body organs, including the brain. However, abnormal accumulation of trace metals in the brain and dyshomeostasis in the different regions of the brain have emerged as contributing factors in neuronal degeneration, Aβ aggregation, and Tau formation. The link between these essential trace metal ions and the risk of AD has been widely studied, although the conclusions have been ambiguous. Despite the absence of evidence for any clinical benefit, therapeutic chelation is still hypothesized to be a therapeutic option for AD. Furthermore, the parameters like bioavailability, ability to cross the BBB, and chelation specificity must be taken into consideration while selecting a suitable chelation therapy. The data in this review summarizes that the primary intervention in AD is brain metal homeostasis along with brain metal scavenging. This review evaluates the impact of different trace metals (Cu, Zn, Fe) on normal brain functioning and their association with neurodegeneration in AD. Also, it investigates the therapeutic potential of metal chelators in the management of AD. An extensive literature search was carried out on the “Web of Science, PubMed, Science Direct, and Google Scholar” to investigate the effect of trace elements in neurological impairment and the role of metal chelators in AD. In addition, the current review highlights the advantages and limitations of chelation therapies and the difficulties involved in developing selective metal chelation therapy in AD patients.
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The authors acknowledge the financial support provided by the Core Research Grant of DST SERB, Government of India (CRG/2020/003316). The authors are also thankful to Shobhaben Pratapbhai Patel School of Pharmacy & Technology Management, SVKM’s NMIMS for providing the infrastructure facility.
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Ginpreet Kaur and Harpal S. Buttar visualized the presented idea and supervised the project. Vinay Chaudhari, Shubhangi Gupta, Siddhi Bagwe-Parab, and Amisha Vora contributed in doing literature searches and preparing the manuscript draft. Ginpreet Kaur and Harpal S Buttar revised and approved the manuscript. All authors contributed to the article and approved the submitted version.
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Chaudhari, V., Bagwe-Parab, S., Buttar, H.S. et al. Challenges and Opportunities of Metal Chelation Therapy in Trace Metals Overload-Induced Alzheimer’s Disease. Neurotox Res 41, 270–287 (2023). https://doi.org/10.1007/s12640-023-00634-7
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DOI: https://doi.org/10.1007/s12640-023-00634-7