TY - JOUR
T1 - Polyphenols as Potential Metal Chelation Compounds against Alzheimer's Disease
AU - Lakey-Beitia, Johant
AU - Burillo, Andrea M.
AU - La Penna, Giovanni
AU - Hegde, Muralidhar L.
AU - Rao, K. S.
N1 - Funding Information:
The authors acknowledge research fundings by: National Secretariat for Science, Technology, and Innovation of Panama (SENACYT) grant number [FID17–002], INDICASAT Internal Grant [JR04-2020] to KSR and National Institute of Neurological Disorders and Stroke (NINDS) of the National Institute of Health (NIH) grant R01NS088645 to MLH. The content is solely the responsibility of the authors
Publisher Copyright:
© 2021 - IOS Press. All rights reserved.
PY - 2021
Y1 - 2021
N2 - 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.
AB - 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.
KW - Alzheimer's disease
KW - amyloid-β
KW - copper
KW - iron
KW - metal chelation therapy
KW - metalloproteins
KW - polyphenols
KW - zinc
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U2 - 10.3233/JAD-200185
DO - 10.3233/JAD-200185
M3 - Review article
C2 - 32568200
AN - SCOPUS:85111118368
SN - 1387-2877
VL - 82
SP - S335-S357
JO - Journal of Alzheimer's Disease
JF - Journal of Alzheimer's Disease
IS - s1
ER -