CuII Binding Properties of N-Truncated Aβ Peptides: In Search of Biological Function
- PMID: 31304745
- DOI: 10.1021/acs.inorgchem.9b01399
CuII Binding Properties of N-Truncated Aβ Peptides: In Search of Biological Function
Abstract
As life expectancy increases, the number of people affected by progressive and irreversible dementia, Alzheimer's Disease (AD), is predicted to grow. No drug designs seem to be working in humans, apparently because the origins of AD have not been identified. Invoking amyloid cascade, metal ions, and ROS production hypothesis of AD, herein we share our point of view on Cu(II) binding properties of Aβ4-x, the most prevalent N-truncated Aβ peptide, currently known as the main constituent of amyloid plaques. The capability of Aβ4-x to rapidly take over copper from previously tested Aβ1-x peptides and form highly stable complexes, redox unreactive and resistant to copper exchange reactions, prompted us to propose physiological roles for these peptides. We discuss the new findings on the reactivity of Cu(II)Aβ4-x with coexisting biomolecules in the context of synaptic cleft; we suggest that the role of Aβ4-x peptides is to quench Cu(II) toxicity in the brain and maintain neurotransmission.
Similar articles
-
Using N-Terminal Coordination of Cu(II) and Ni(II) to Isolate the Coordination Environment of Cu(I) and Cu(II) Bound to His13 and His14 in Amyloid-β(4-16).Inorg Chem. 2019 Nov 18;58(22):15138-15154. doi: 10.1021/acs.inorgchem.9b01940. Epub 2019 Oct 28. Inorg Chem. 2019. PMID: 31657204
-
Oxidase Reactivity of CuII Bound to N-Truncated Aβ Peptides Promoted by Dopamine.Int J Mol Sci. 2021 May 14;22(10):5190. doi: 10.3390/ijms22105190. Int J Mol Sci. 2021. PMID: 34068879 Free PMC article.
-
Resistance of Cu(Aβ4-16) to Copper Capture by Metallothionein-3 Supports a Function for the Aβ4-42 Peptide as a Synaptic Cu(II) Scavenger.Angew Chem Int Ed Engl. 2016 Jul 11;55(29):8235-8. doi: 10.1002/anie.201511968. Epub 2016 May 30. Angew Chem Int Ed Engl. 2016. PMID: 27238224
-
Mutual interference of Cu and Zn ions in Alzheimer's disease: perspectives at the molecular level.Dalton Trans. 2017 Oct 14;46(38):12750-12759. doi: 10.1039/c7dt01344b. Epub 2017 Sep 22. Dalton Trans. 2017. PMID: 28937157 Free PMC article. Review.
-
Cu and Zn interactions with Aβ peptides: consequence of coordination on aggregation and formation of neurotoxic soluble Aβ oligomers.Metallomics. 2019 Jan 23;11(1):64-84. doi: 10.1039/c8mt00203g. Metallomics. 2019. PMID: 30234208 Review.
Cited by
-
Nerve Growth Factor Peptides Bind Copper(II) with High Affinity: A Thermodynamic Approach to Unveil Overlooked Neurotrophin Roles.Int J Mol Sci. 2021 May 11;22(10):5085. doi: 10.3390/ijms22105085. Int J Mol Sci. 2021. PMID: 34064906 Free PMC article.
-
Bioinorganic Chemistry of Micronutrients Related to Alzheimer's and Parkinson's Diseases.Molecules. 2023 Jul 17;28(14):5467. doi: 10.3390/molecules28145467. Molecules. 2023. PMID: 37513339 Free PMC article. Review.
-
Novel Perspective on Alzheimer's Disease Treatment: Rosmarinic Acid Molecular Interplay with Copper(II) and Amyloid β.Life (Basel). 2020 Jul 20;10(7):118. doi: 10.3390/life10070118. Life (Basel). 2020. PMID: 32698429 Free PMC article.
-
MAD-microbial (origin of) Alzheimer's disease hypothesis: from infection and the antimicrobial response to disruption of key copper-based systems.Front Neurosci. 2024 Oct 2;18:1467333. doi: 10.3389/fnins.2024.1467333. eCollection 2024. Front Neurosci. 2024. PMID: 39416952 Free PMC article. Review.
-
Copper(II) partially protects three histidine residues and the N-terminus of amyloid-β peptide from diethyl pyrocarbonate (DEPC) modification.FEBS Open Bio. 2020 Jun;10(6):1072-1081. doi: 10.1002/2211-5463.12857. Epub 2020 Apr 29. FEBS Open Bio. 2020. PMID: 32255544 Free PMC article.
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical
Research Materials