Phytic acid as a potential treatment for Alzheimer's pathology: Evidence from animal and in vitro models

Thimmappa S. Anekonda, Teri L. Wadsworth, Robert Sabin, Kate Frahler, Christopher Harris, Babett Petriko, Martina Ralle, Randall (Randy) Woltjer, Joseph Quinn

Research output: Contribution to journalArticle

33 Citations (Scopus)

Abstract

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.

Original languageEnglish (US)
Pages (from-to)21-35
Number of pages15
JournalJournal of Alzheimer's Disease
Volume23
Issue number1
DOIs
StatePublished - 2011

Fingerprint

Phytic Acid
Pathology
Alzheimer Disease
AMP-Activated Protein Kinases
Autophagy
Brain
Amyloid
Copper
Iron
Sirtuin 1
Cytochromes a
In Vitro Techniques
Ceruloplasmin
Phytochemicals
Electron Transport Complex IV
Protein Transport
Protein C
Superoxides
Drinking Water
Hydrogen Peroxide

Keywords

  • Amyloid-β
  • amyloid-β protein precursor
  • antioxidant
  • autophagy
  • beclin-1
  • phosphorylated AMP-activated protein kinase
  • sirtuin 1

ASJC Scopus subject areas

  • Psychiatry and Mental health
  • Geriatrics and Gerontology
  • Clinical Psychology

Cite this

Phytic acid as a potential treatment for Alzheimer's pathology : Evidence from animal and in vitro models. / Anekonda, Thimmappa S.; Wadsworth, Teri L.; Sabin, Robert; Frahler, Kate; Harris, Christopher; Petriko, Babett; Ralle, Martina; Woltjer, Randall (Randy); Quinn, Joseph.

In: Journal of Alzheimer's Disease, Vol. 23, No. 1, 2011, p. 21-35.

Research output: Contribution to journalArticle

Anekonda, Thimmappa S. ; Wadsworth, Teri L. ; Sabin, Robert ; Frahler, Kate ; Harris, Christopher ; Petriko, Babett ; Ralle, Martina ; Woltjer, Randall (Randy) ; Quinn, Joseph. / Phytic acid as a potential treatment for Alzheimer's pathology : Evidence from animal and in vitro models. In: Journal of Alzheimer's Disease. 2011 ; Vol. 23, No. 1. pp. 21-35.
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