Rebalancing β-Amyloid-Induced Decrease of ATP Level by Amorphous Nano/Micro Polyphosphate: Suppression of the Neurotoxic Effect of Amyloid β-Protein Fragment 25-35
Morbus Alzheimer neuropathology is characterized by an impaired energy homeostasis of brain tissue. We present an approach towards a potential therapy of Alzheimer disease based on the high-energy polymer inorganic polyphosphate (polyP), which physiologically occurs both in the extracellular and in...
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| Format: | Article |
| Language: | English |
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MDPI AG
2017-10-01
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| Series: | International Journal of Molecular Sciences |
| Subjects: | |
| Online Access: | https://www.mdpi.com/1422-0067/18/10/2154 |
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Article |
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DOAJ |
| language |
English |
| format |
Article |
| sources |
DOAJ |
| author |
Werner E. G. Müller Shunfeng Wang Maximilian Ackermann Meik Neufurth Renate Steffen Egherta Mecja Rafael Muñoz-Espí Qingling Feng Heinz C. Schröder Xiaohong Wang |
| spellingShingle |
Werner E. G. Müller Shunfeng Wang Maximilian Ackermann Meik Neufurth Renate Steffen Egherta Mecja Rafael Muñoz-Espí Qingling Feng Heinz C. Schröder Xiaohong Wang Rebalancing β-Amyloid-Induced Decrease of ATP Level by Amorphous Nano/Micro Polyphosphate: Suppression of the Neurotoxic Effect of Amyloid β-Protein Fragment 25-35 International Journal of Molecular Sciences β-amyloid calcium polyphosphate microparticles neurotoxic effect adenosine triphosphate level PC12 cells primary rat cortex neurons |
| author_facet |
Werner E. G. Müller Shunfeng Wang Maximilian Ackermann Meik Neufurth Renate Steffen Egherta Mecja Rafael Muñoz-Espí Qingling Feng Heinz C. Schröder Xiaohong Wang |
| author_sort |
Werner E. G. Müller |
| title |
Rebalancing β-Amyloid-Induced Decrease of ATP Level by Amorphous Nano/Micro Polyphosphate: Suppression of the Neurotoxic Effect of Amyloid β-Protein Fragment 25-35 |
| title_short |
Rebalancing β-Amyloid-Induced Decrease of ATP Level by Amorphous Nano/Micro Polyphosphate: Suppression of the Neurotoxic Effect of Amyloid β-Protein Fragment 25-35 |
| title_full |
Rebalancing β-Amyloid-Induced Decrease of ATP Level by Amorphous Nano/Micro Polyphosphate: Suppression of the Neurotoxic Effect of Amyloid β-Protein Fragment 25-35 |
| title_fullStr |
Rebalancing β-Amyloid-Induced Decrease of ATP Level by Amorphous Nano/Micro Polyphosphate: Suppression of the Neurotoxic Effect of Amyloid β-Protein Fragment 25-35 |
| title_full_unstemmed |
Rebalancing β-Amyloid-Induced Decrease of ATP Level by Amorphous Nano/Micro Polyphosphate: Suppression of the Neurotoxic Effect of Amyloid β-Protein Fragment 25-35 |
| title_sort |
rebalancing β-amyloid-induced decrease of atp level by amorphous nano/micro polyphosphate: suppression of the neurotoxic effect of amyloid β-protein fragment 25-35 |
| publisher |
MDPI AG |
| series |
International Journal of Molecular Sciences |
| issn |
1422-0067 |
| publishDate |
2017-10-01 |
| description |
Morbus Alzheimer neuropathology is characterized by an impaired energy homeostasis of brain tissue. We present an approach towards a potential therapy of Alzheimer disease based on the high-energy polymer inorganic polyphosphate (polyP), which physiologically occurs both in the extracellular and in the intracellular space. Rat pheochromocytoma (PC) 12 cells, as well as rat primary cortical neurons were exposed to the Alzheimer peptide Aβ25-35. They were incubated in vitro with polyphosphate (polyP); ortho-phosphate was used as a control. The polymer remained as Na+ salt; or complexed in a stoichiometric ratio to Ca2+ (Na-polyP[Ca2+]); or was processed as amorphous Ca-polyP microparticles (Ca-polyP-MP). Ortho-phosphate was fabricated as crystalline Ca-phosphate nanoparticles (Ca-phosphate-NP). We show that the pre-incubation of PC12 cells and primary cortical neurons with polyP protects the cells against the neurotoxic effect of the Alzheimer peptide Aβ25-35. The strongest effect was observed with amorphous polyP microparticles (Ca-polyP-MP). The effect of the soluble sodium salt; Na-polyP (Na-polyP[Ca2+]) was lower; while crystalline orthophosphate nanoparticles (Ca-phosphate-NP) were ineffective. Ca-polyP-MP microparticles and Na-polyP[Ca2+] were found to markedly enhance the intracellular ATP level. Pre-incubation of Aβ25-35 during aggregate formation, with the polyP preparation before exposure of the cells, had a small effect on neurotoxicity. We conclude that recovery of the compromised energy status in neuronal cells by administration of nontoxic biodegradable Ca-salts of polyP reverse the β-amyloid-induced decrease of adenosine triphosphate (ATP) level. This study contributes to a new routes for a potential therapeutic intervention in Alzheimer’s disease pathophysiology. |
| topic |
β-amyloid calcium polyphosphate microparticles neurotoxic effect adenosine triphosphate level PC12 cells primary rat cortex neurons |
| url |
https://www.mdpi.com/1422-0067/18/10/2154 |
| work_keys_str_mv |
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1725193122670968832 |
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doaj-d298f60baeaa4aef98ffa1234c62cfc12020-11-25T01:05:47ZengMDPI AGInternational Journal of Molecular Sciences1422-00672017-10-011810215410.3390/ijms18102154ijms18102154Rebalancing β-Amyloid-Induced Decrease of ATP Level by Amorphous Nano/Micro Polyphosphate: Suppression of the Neurotoxic Effect of Amyloid β-Protein Fragment 25-35Werner E. G. Müller0Shunfeng Wang1Maximilian Ackermann2Meik Neufurth3Renate Steffen4Egherta Mecja5Rafael Muñoz-Espí6Qingling Feng7Heinz C. Schröder8Xiaohong Wang9ERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, GermanyERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, GermanyInstitute of Functional and Clinical Anatomy, University Medical Center of the Johannes Gutenberg University, Johann Joachim Becher Weg 13, D-55099 Mainz, GermanyERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, GermanyERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, GermanyERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, GermanyInstitute of Materials Science (ICMUV), Universitat de València, C/Catedràtic José Beltrán 2, 46980 Paterna, València, SpainKey Laboratory of Advanced Materials of Ministry of Education of China, School of Materials Science and Engineering, Tsinghua University, Beijing 100084, ChinaERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, GermanyERC Advanced Investigator Grant Research Group at the Institute for Physiological Chemistry, University Medical Center of the Johannes Gutenberg University, Duesbergweg 6, D-55128 Mainz, GermanyMorbus Alzheimer neuropathology is characterized by an impaired energy homeostasis of brain tissue. We present an approach towards a potential therapy of Alzheimer disease based on the high-energy polymer inorganic polyphosphate (polyP), which physiologically occurs both in the extracellular and in the intracellular space. Rat pheochromocytoma (PC) 12 cells, as well as rat primary cortical neurons were exposed to the Alzheimer peptide Aβ25-35. They were incubated in vitro with polyphosphate (polyP); ortho-phosphate was used as a control. The polymer remained as Na+ salt; or complexed in a stoichiometric ratio to Ca2+ (Na-polyP[Ca2+]); or was processed as amorphous Ca-polyP microparticles (Ca-polyP-MP). Ortho-phosphate was fabricated as crystalline Ca-phosphate nanoparticles (Ca-phosphate-NP). We show that the pre-incubation of PC12 cells and primary cortical neurons with polyP protects the cells against the neurotoxic effect of the Alzheimer peptide Aβ25-35. The strongest effect was observed with amorphous polyP microparticles (Ca-polyP-MP). The effect of the soluble sodium salt; Na-polyP (Na-polyP[Ca2+]) was lower; while crystalline orthophosphate nanoparticles (Ca-phosphate-NP) were ineffective. Ca-polyP-MP microparticles and Na-polyP[Ca2+] were found to markedly enhance the intracellular ATP level. Pre-incubation of Aβ25-35 during aggregate formation, with the polyP preparation before exposure of the cells, had a small effect on neurotoxicity. We conclude that recovery of the compromised energy status in neuronal cells by administration of nontoxic biodegradable Ca-salts of polyP reverse the β-amyloid-induced decrease of adenosine triphosphate (ATP) level. This study contributes to a new routes for a potential therapeutic intervention in Alzheimer’s disease pathophysiology.https://www.mdpi.com/1422-0067/18/10/2154β-amyloidcalcium polyphosphatemicroparticlesneurotoxic effectadenosine triphosphate levelPC12 cellsprimary rat cortex neurons |