Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease
The natural element aluminum possesses a number of unique biochemical and biophysical properties that make this highly neurotoxic species deleterious towards the structural integrity, conformation, reactivity and stability of several important biomolecules. These include aluminum’s <b>(i)</...
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MDPI AG
2022-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/16/5123 |
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| author | Yuhai Zhao Aileen I. Pogue Peter N. Alexandrov Leslie G. Butler Wenhong Li Vivian R. Jaber Walter J. Lukiw |
| author_facet | Yuhai Zhao Aileen I. Pogue Peter N. Alexandrov Leslie G. Butler Wenhong Li Vivian R. Jaber Walter J. Lukiw |
| author_sort | Yuhai Zhao |
| collection | DOAJ |
| description | The natural element aluminum possesses a number of unique biochemical and biophysical properties that make this highly neurotoxic species deleterious towards the structural integrity, conformation, reactivity and stability of several important biomolecules. These include aluminum’s <b>(i)</b> small ionic size and highly electrophilic nature, having the highest charge density of any metallic cation with a Z<sup>2</sup>/r of 18 (ionic charge +3, radius 0.5 nm); <b>(ii)</b> inclination to form extremely stable electrostatic bonds with a tendency towards covalency; <b>(iii)</b> ability to interact irreversibly and/or significantly slow down the exchange-rates of complex aluminum–biomolecular interactions; <b>(iv)</b> extremely dense electropositive charge with one of the highest known affinities for oxygen-donor ligands such as phosphate; <b>(v)</b> presence as the most abundant metal in the Earth’s biosphere and general bioavailability in drinking water, food, medicines, consumer products, groundwater and atmospheric dust; and <b>(vi)</b> abundance as one of the most commonly encountered intracellular and extracellular metallotoxins. Despite aluminum’s prevalence and abundance in the biosphere it is remarkably well-tolerated by all plant and animal species; no organism is known to utilize aluminum metabolically; however, a biological role for aluminum has been assigned in the compaction of chromatin. In this Communication, several examples are given where aluminum has been shown to irreversibly perturb and/or stabilize the natural conformation of biomolecules known to be important in energy metabolism, gene expression, cellular homeostasis and pathological signaling in neurological disease. Several neurodegenerative disorders that include the tauopathies, Alzheimer’s disease and multiple prion disorders involve the altered conformation of naturally occurring cellular proteins. Based on the data currently available we speculate that one way aluminum contributes to neurological disease is to induce the misfolding of naturally occurring proteins into altered pathological configurations that contribute to the neurodegenerative disease process. |
| first_indexed | 2024-03-09T04:02:48Z |
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| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T04:02:48Z |
| publishDate | 2022-08-01 |
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| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b0289517bf6e4be7b325650dfdc91af22023-12-03T14:10:59ZengMDPI AGMolecules1420-30492022-08-012716512310.3390/molecules27165123Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding DiseaseYuhai Zhao0Aileen I. Pogue1Peter N. Alexandrov2Leslie G. Butler3Wenhong Li4Vivian R. Jaber5Walter J. Lukiw6LSU Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USAAlchem Biotek Research, Toronto, ON M5S 1A8, CanadaRussian Academy of Medical Sciences, 113152 Moscow, RussianDepartment of Chemistry, Louisiana State University, Baton Rouge, LA 70803, USADepartment of Pharmacology, Jiangxi University of TCM, Nanchang 330004, ChinaLSU Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USALSU Neuroscience Center, Louisiana State University Health Science Center, New Orleans, LA 70112, USAThe natural element aluminum possesses a number of unique biochemical and biophysical properties that make this highly neurotoxic species deleterious towards the structural integrity, conformation, reactivity and stability of several important biomolecules. These include aluminum’s <b>(i)</b> small ionic size and highly electrophilic nature, having the highest charge density of any metallic cation with a Z<sup>2</sup>/r of 18 (ionic charge +3, radius 0.5 nm); <b>(ii)</b> inclination to form extremely stable electrostatic bonds with a tendency towards covalency; <b>(iii)</b> ability to interact irreversibly and/or significantly slow down the exchange-rates of complex aluminum–biomolecular interactions; <b>(iv)</b> extremely dense electropositive charge with one of the highest known affinities for oxygen-donor ligands such as phosphate; <b>(v)</b> presence as the most abundant metal in the Earth’s biosphere and general bioavailability in drinking water, food, medicines, consumer products, groundwater and atmospheric dust; and <b>(vi)</b> abundance as one of the most commonly encountered intracellular and extracellular metallotoxins. Despite aluminum’s prevalence and abundance in the biosphere it is remarkably well-tolerated by all plant and animal species; no organism is known to utilize aluminum metabolically; however, a biological role for aluminum has been assigned in the compaction of chromatin. In this Communication, several examples are given where aluminum has been shown to irreversibly perturb and/or stabilize the natural conformation of biomolecules known to be important in energy metabolism, gene expression, cellular homeostasis and pathological signaling in neurological disease. Several neurodegenerative disorders that include the tauopathies, Alzheimer’s disease and multiple prion disorders involve the altered conformation of naturally occurring cellular proteins. Based on the data currently available we speculate that one way aluminum contributes to neurological disease is to induce the misfolding of naturally occurring proteins into altered pathological configurations that contribute to the neurodegenerative disease process.https://www.mdpi.com/1420-3049/27/16/5123aluminumAlzheimer’s disease (AD)biomoleculesadenosine triphosphate (ATP)histone linker proteins (H1 class)prion disease (PrD) |
| spellingShingle | Yuhai Zhao Aileen I. Pogue Peter N. Alexandrov Leslie G. Butler Wenhong Li Vivian R. Jaber Walter J. Lukiw Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease Molecules aluminum Alzheimer’s disease (AD) biomolecules adenosine triphosphate (ATP) histone linker proteins (H1 class) prion disease (PrD) |
| title | Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease |
| title_full | Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease |
| title_fullStr | Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease |
| title_full_unstemmed | Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease |
| title_short | Alteration of Biomolecular Conformation by Aluminum-Implications for Protein Misfolding Disease |
| title_sort | alteration of biomolecular conformation by aluminum implications for protein misfolding disease |
| topic | aluminum Alzheimer’s disease (AD) biomolecules adenosine triphosphate (ATP) histone linker proteins (H1 class) prion disease (PrD) |
| url | https://www.mdpi.com/1420-3049/27/16/5123 |
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