Document Detail


Phytic acid as a potential treatment for alzheimer's pathology: evidence from animal and in vitro models.
MedLine Citation:
PMID:  20930278     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
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:
Type:  Journal Article; Research Support, N.I.H., Extramural    
Journal Detail:
Title:  Journal of Alzheimer's disease : JAD     Volume:  23     ISSN:  1875-8908     ISO Abbreviation:  J. Alzheimers Dis.     Publication Date:  2011  
Date Detail:
Created Date:  2011-01-13     Completed Date:  2011-05-05     Revised Date:  2014-03-20    
Medline Journal Info:
Nlm Unique ID:  9814863     Medline TA:  J Alzheimers Dis     Country:  Netherlands    
Other Details:
Languages:  eng     Pagination:  21-35     Citation Subset:  IM    
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MeSH Terms
Descriptor/Qualifier:
Adenosine Triphosphate / 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:
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 EY018708-01A2/EY/NEI NIH HHS; T32 AT002688-05/AT/NCCAM NIH HHS
Chemical
Reg. No./Substance:
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 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

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