Challenges Associated with Metal Chelation Therapy in Alzheimer's Disease

Article type: Review Article

Authors: Hegde, Muralidhar L.^a; | Bharathi, P.^a | Suram, Anitha^a | Venugopal, Chitra^b | Jagannathan, Ramya^c | Poddar, Pankaj^c | Srinivas, Pullabhatla^d | Sambamurti, Kumar^b | Rao, Kosagisharaf Jagannatha^a | Scancar, Janez^e | Messori, Luigi^f | Zecca, Luigi^g | Zatta, Paolo^{h; *}

Affiliations: [a] Department of Biochemistry and Nutrition, Central Food Technological Research Institute, Mysore, India | [b] Department of Neuroscience, Medical University of South Carolina, Charleston, SC, USA | [c] Physical & Materials Chemistry Division, National Chemical Laboratory, Pune, India | [d] Plantation Products & Spice Flavour Technology, Central Food Technological Research Institute, Mysore, India | [e] Department of Environmental Sciences, Jozef Stefan Institute, Jamova, Ljubljana, Slovenia | [f] Department of Chemistry, University of Florence, Sesto Fiorentino, Firenze, Italy | [g] CNR-Institute for Biomedical Technologies, Segrate (Milano), Italy | [h] CNR-Institute for Biomedical Technologies-Metalloprotein Unit, Department of Biology University of Padova, Padova, Italy

Correspondence: [*] Corresponding author: Dr. Paolo Zatta, CNR-Institute for Biomedical Technologies-Metalloprotein Unit, Department of Biology University of Padova, Viale G. Colombo 3, 35121 Padova, Italy. Tel.: +39 049 8276331; Fax: +39 049 8276330; E-mail: [email protected].

Note: [1] Present address: Department of Cell and Molecular Biology, University of Texas Medical Branch (UTMB), Galveston, Texas, USA.

Abstract: A close association between brain metal dishomeostasis and the onset and/or progression of Alzheimer's disease (AD) has been clearly established in a number of studies, although the underlying biochemical mechanisms remain obscure. This observation renders chelation therapy an attractive pharmacological option for the treatment of this disease. However, a number of requirements must be fulfilled in order to adapt chelation therapy to AD so that the term “metal targeted strategies” seems now more appropriate. Indeed, brain metal redistribution rather than brain metal scavenging and removal is the major goal of this type of intervention. The most recent developments in metal targeted strategies for AD will be discussed using, as useful examples, clioquinol, curcumin, and epigallocatechin, and the future perspectives will also be outlined.

Keywords: Alzheimer's disease, clioquinol, cuprizone, metal dishomeostasis, metal ions, nanomedicine, Parkinson's disease, polyphenols

DOI: 10.3233/JAD-2009-1068

Journal: Journal of Alzheimer's Disease, vol. 17, no. 3, pp. 457-468, 2009