|Phytic acid as a potential treatment for alzheimer's pathology: evidence from animal and in vitro models.|
|PMID: 20930278 Owner: NLM Status: MEDLINE|
|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.|
|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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|Type: Journal Article; Research Support, N.I.H., Extramural|
|Title: Journal of Alzheimer's disease : JAD Volume: 23 ISSN: 1875-8908 ISO Abbreviation: J. Alzheimers Dis. Publication Date: 2011|
|Created Date: 2011-01-13 Completed Date: 2011-05-05 Revised Date: 2014-09-21|
Medline Journal Info:
|Nlm Unique ID: 9814863 Medline TA: J Alzheimers Dis Country: Netherlands|
|Languages: eng Pagination: 21-35 Citation Subset: IM|
|APA/MLA Format Download EndNote Download BibTex|
Alzheimer Disease / drug therapy*, pathology*
Amyloid beta-Peptides / metabolism
Analysis of Variance
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
Gene Expression Regulation / drug effects
Hydrogen Peroxide / pharmacology
Malondialdehyde / metabolism
Mice, Inbred C57BL
Phytic Acid / therapeutic use*
Sirtuins / metabolism
|1S10RR025512-01/RR/NCRR NIH HHS; 5R21 EY018708-02/EY/NEI NIH HHS; P30 AG008017/AG/NIA NIH HHS; P30AG008017/AG/NIA NIH HHS; R21 EY018708/EY/NEI NIH HHS; R21 EY018708-01A2/EY/NEI NIH HHS; T32 AT002688-05/AT/NCCAM NIH HHS|
|0/Amyloid beta-Peptides; 0/Antipsychotic Agents; 0/Apoptosis Regulatory Proteins; 0/Becn1 protein, mouse; 4Y8F71G49Q/Malondialdehyde; 7IGF0S7R8I/Phytic Acid; 8L70Q75FXE/Adenosine Triphosphate; BBX060AN9V/Hydrogen Peroxide; EC 188.8.131.52/Cyclooxygenase 1; EC 184.108.40.206/Ceruloplasmin; EC 220.127.116.11/Electron Transport Complex IV; EC 3.5.1.-/Sirtuins|
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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