1. Academic Validation
  2. Vitamin D Attenuates Alzheimer-like Pathology Induced by Okadaic Acid

Vitamin D Attenuates Alzheimer-like Pathology Induced by Okadaic Acid

  • ACS Chem Neurosci. 2021 Apr 21;12(8):1343-1350. doi: 10.1021/acschemneuro.0c00812.
Yiming Pan 1 Yalin Zhang 1 Ning Liu 1 Wanyi Lu 1 Jingxin Yang 1 Ye Li 1 Zuwang Liu 1 Yinghong Wei 1 Yan Lou 2 Juan Kong 1
Affiliations

Affiliations

  • 1 Department of Clinical Nutrition, Shengjing Hospital of China Medical University, Shenyang 110004, China.
  • 2 Department of Computer Science, China Medical University, Shenyang 110013, China.
Abstract

Many elderly individuals suffer from Alzheimer's disease (AD), which causes a growing concern. We investigated the mechanism underlying the effects of vitamin D (VD) as a prophylactic treatment. A mouse model of okadaic-acid-induced AD-like pathology was used in vivo and in vitro. Morris water maze and field trials were used to assess cognitive function. The expression levels of VDR, MTHFR, LCMT-1, PP2A, p-TAU (Thr396), and T-TAU and the methylation level of PP2A were measured by Western blotting, and a reversal of the increase in the levels of these proteins in an AD cell model was observed. We used MTHFR-knockdown SH-SY5Y cells to further test the effects of VD, treated these cells with cycloheximide and MG132, and used RT-PCR to explore the mechanism underlying MTHFR targeting. We found that the effects of VD on AD were impaired by MTHFR knockdown through a pretranscriptional mechanism. In addition, VD attenuated AD-induced cognitive impairment and significantly suppressed the expression of TAU. Our findings indicated that VD treatment alleviated TAU accumulation and rescued methylated PP2A by increasing the expression of LCMT-1 and MTHFR.

Keywords

Alzheimer’s disease; CCE; PP2A methylation; vitamin D.

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