| Phytic acid as a potential treatment for alzheimer's pathology: evidence from animal and in vitro models. | |
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MedLine Citation:
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PMID: 20930278 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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Alzheimer's disease (AD) causes progressive, age-dependent cortical and hippocampal dysfunction leading to abnormal intellectual capacity and memory. We propose a novel protective treatment for AD pathology with phytic acid (inositol hexakisphosphate), a phytochemical found in food grains and a key signaling molecule in mammalian cells. We evaluated the protective and beneficial effects of phytic acid against amyloid-β (Aβ) pathology in MC65 cells and the Tg2576 mouse model. In MC65 cells, 48-72-hour treatment with phytic acid provided complete protection against amyloid precursor protein-C-terminal fragment-induced cytotoxicity by attenuating levels of increased intracellular calcium, hydrogen peroxide, superoxide, Aβ oligomers, and moderately upregulated the expression of autophagy (beclin-1) protein. In a tolerance paradigm, wild type mice were treated with 2% phytic acid in drinking water for 70 days. Phytic acid was well tolerated. Ceruloplasmin activity, brain copper and iron levels, and brain superoxide dismutase and ATP levels were unaffected by the treatment. There was a significant increase in brain levels of cytochrome oxidase and a decrease in lipid peroxidation with phytic acid administration. In a treatment paradigm, 12-month old Tg2576 and wild type mice were treated with 2% phytic acid or vehicle for 6 months. Brain levels of copper, iron, and zinc were unaffected. The effects of phytic acid were modest on the expression of AβPP trafficking-associated protein AP180, autophagy-associated proteins (beclin-1, LC3B), sirtuin 1, the ratio of phosphorylated AMP-activated protein kinase (PAMPK) to AMPK, soluble Aβ1-40, and insoluble Aβ1-42. These results suggest that phytic acid may provide a viable treatment option for AD. |
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Authors:
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Thimmappa S Anekonda; Teri L Wadsworth; Robert Sabin; Kate Frahler; Christopher Harris; Babett Petriko; Martina Ralle; Randy Woltjer; Joseph F Quinn |
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Publication Detail:
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Type: Journal Article; Research Support, N.I.H., Extramural |
Journal Detail:
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Title: Journal of Alzheimer's disease : JAD Volume: 23 ISSN: 1875-8908 ISO Abbreviation: J. Alzheimers Dis. Publication Date: 2011 |
Date Detail:
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Created Date: 2011-01-13 Completed Date: 2011-05-05 Revised Date: 2011-08-19 |
Medline Journal Info:
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Nlm Unique ID: 9814863 Medline TA: J Alzheimers Dis Country: Netherlands |
Other Details:
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Languages: eng Pagination: 21-35 Citation Subset: IM |
Affiliation:
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Department of Neurology, Oregon Health & Science University, Portland, OR 97239, USA. anekondt@ohsu.edu |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Adenosine Triphosphate
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metabolism Alzheimer Disease / drug therapy*, pathology* Amyloid beta-Peptides / metabolism Analysis of Variance Animals Antipsychotic Agents / therapeutic use* Apoptosis Regulatory Proteins / metabolism Autophagy / drug effects Body Weight / drug effects Cell Line, Tumor Ceruloplasmin / metabolism Cyclooxygenase 1 / metabolism Disease Models, Animal Dose-Response Relationship, Drug Electron Transport Complex IV / metabolism Enzyme-Linked Immunosorbent Assay / methods Female Gene Expression Regulation / drug effects Humans Hydrogen Peroxide / pharmacology Malondialdehyde / metabolism Mice Mice, Inbred C57BL Mice, Transgenic Neuroblastoma Phytic Acid / therapeutic use* Sirtuins / metabolism Time Factors |
| Grant Support | |
ID/Acronym/Agency:
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1S10RR025512-01/RR/NCRR NIH HHS; 5R21 EY018708-02/EY/NEI NIH HHS; P30AG008017/AG/NIA NIH HHS; R21 EY018708-01A2/EY/NEI NIH HHS; T32 AT002688-05/AT/NCCAM NIH HHS |
| Chemical | |
Reg. No./Substance:
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0/Amyloid beta-Peptides; 0/Antipsychotic Agents; 0/Apoptosis Regulatory Proteins; 0/Becn1 protein, mouse; 542-78-9/Malondialdehyde; 56-65-5/Adenosine Triphosphate; 7722-84-1/Hydrogen Peroxide; 83-86-3/Phytic Acid; EC 1.14.99.1/Cyclooxygenase 1; EC 1.16.3.1/Ceruloplasmin; EC 1.9.3.1/Electron Transport Complex IV; EC 3.5.1.-/Sirtuins |
| Comments/Corrections | |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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