Polyphenols as Potential Metal Chelation Compounds Against Alzheimer’s Disease

Issue title: Translational Research and Drug Discovery for Neurodegeneration: Challenges for Latin America

Guest editors: K.S. Jagannatha Rao, Gabrielle B. Britton, Luisa Lilia Rocha Arrieta, Norberto Garcia-Cairasco, Alberto Lazarowski, Adrián Palacios, Antoni Camins Espuny and Ricardo B. Maccioni

Article type: Review Article

Authors: Lakey-Beitia, Johant^a | Burillo, Andrea M.^a | La Penna, Giovanni^b | Hegde, Muralidhar L.^{c; d; e} | Rao, K.S.^{f; g; *}

Affiliations: [a] Centre for Biodiversity and Drug Discovery, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, Panama | [b] National Research Council, Institute of Chemistry of Organometallic Compounds, Sesto Fiorentino (FI), Italy | [c] Department of Radiation Oncology, Houston Methodist Research Institute, Houston, TX, USA | [d] Department of Neurosurgery, Center for Neuroregeneration, Houston Methodist Research Institute, Houston, TX, USA | [e] Weill Medical College of Cornell University, New York, NY, USA | [f] Centre for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, Panama | [g] Zhongke Jianlan Medical Institute, Hangzhou, People’s Republic of China

Correspondence: [*] Correspondence to: K.S Rao, PhD, Centre for Neuroscience, Instituto de Investigaciones Científicas y Servicios de Alta Tecnología (INDICASAT AIP), Clayton, City of Knowledge, 0843-01103, Panama. Tel.: +507 517 0700; E-mail: [email protected].

Abstract:  Alzheimer’s disease (AD) is the most common neurodegenerative disease affecting more than 50 million people worldwide. The pathology of this multifactorial disease is primarily characterized by the formation of amyloid-β (Aβ) aggregates; however, other etiological factors including metal dyshomeostasis, specifically copper (Cu), zinc (Zn), and iron (Fe), play critical role in disease progression. Because these transition metal ions are important for cellular function, their imbalance can cause oxidative stress that leads to cellular death and eventual cognitive decay. Importantly, these transition metal ions can interact with the amyloid-β protein precursor (AβPP) and Aβ42 peptide, affecting Aβ aggregation and increasing its neurotoxicity. Considering how metal dyshomeostasis may substantially contribute to AD, this review discusses polyphenols and the underlying chemical principles that may enable them to act as natural chelators. Furthermore, polyphenols have various therapeutic effects, including antioxidant activity, metal chelation, mitochondrial function, and anti-amyloidogenic activity. These combined therapeutic effects of polyphenols make them strong candidates for a moderate chelation-based therapy for AD.

Keywords: Alzheimer’s disease, amyloid-β, metalloproteins, copper, zinc, iron, polyphenols, metal chelation therapy

DOI: 10.3233/JAD-200185

Journal: Journal of Alzheimer's Disease, vol. 82, no. s1, pp. S335-S357, 2021