4.7 Article

High-Phytate Diets Increase Amyloid β Deposition and Apoptotic Neuronal Cell Death in a Rat Model

期刊

NUTRIENTS
卷 13, 期 12, 页码 -

出版社

MDPI
DOI: 10.3390/nu13124370

关键词

high-phytate diet; Ca2+ and Pi dyshomeostasis; amyloid-beta; APP processing; APP; beta-secretases (Bace1); retinoid X receptor

资金

  1. Korean Ministry of Health Welfare [HI14C1135]
  2. Basic Science Research Program [2021R1I1A1A0105142911]
  3. Mid-career Researcher Program [2019R1A2C200813013]
  4. National Research Foundation [NRF-2021R1A5A2030333]

向作者/读者索取更多资源

The study revealed that rats fed high-phytate diets showed A beta accumulation and increased neuronal cell death in the hippocampus, with the activation of the amyloidogenic pathway. Dysregulation of calcium and phosphate homeostasis mediated by phytate is a significant risk factor for elevated A beta accumulation and apoptotic neuronal cell death.
Amyloid-beta (A beta) accumulation in the hippocampus is an essential event in the pathogenesis of Alzheimer's disease. Insoluble A beta is formed through the sequential proteolytic hydrolysis of the A beta precursor protein, which is cleaved by proteolytic secretases. However, the pathophysiological mechanisms of A beta accumulation remain elusive. Here, we report that rats fed high-phytate diets showed A beta accumulation and increased apoptotic neuronal cell death in the hippocampus through the activation of the amyloidogenic pathway in the hippocampus. Immunoblotting and immunohistochemical analyses confirmed that the overexpression of BACE1 beta-secretase, a critical enzyme for A beta generation, exacerbated the hippocampal A beta accumulation in rats fed high-phytate diets. Moreover, we identified that parathyroid hormone, a physiological hormone responding to the phytate-mediated dysregulation of calcium and phosphate homeostasis, plays an essential role in the transcriptional activation of the A beta precursor protein and BACE1 through the vitamin D receptor and retinoid X receptor axis. Thus, our findings suggest that phytate-mediated dysregulation of calcium and phosphate is a substantial risk factor for elevated A beta accumulation and apoptotic neuronal cell death in rats.

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