Aging
Navigate
Submit an Article
Research Paper|Volume 13, Issue 8|pp 11150—11169

The neuroprotection of deproteinized calf blood extractives injection against Alzheimer's disease via regulation of Nrf-2 signaling

Yidi Qu1, Wenqi Wang1, Tianrui Chen3, Yumin Yang1, Yizhi Zhang2, Di Wang1
  • 1School of Life Sciences, Jilin University, Changchun 130012, China
  • 2Department of Neurology, The Second Hospital of Jilin University, Jilin University, Changchun 130041, China
  • 3Department of Bone Tumor Surgery, Changzheng Hospital, Second Military Medical University, Shanghai 200003, China
Received: May 22, 2020Accepted: February 12, 2021Published: March 26, 2021
https://doi.org/10.18632/aging.202776

Copyright: © 2021 Qu et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Alzheimer’s disease (AD) is characterized by cognitive decline due to the accumulation of extracellular β-amyloid (Aβ) plaques and neurofibrillary tangles in the brain, which impair glutamate (Glu) metabolism. Deproteinized Calf Blood Extractive Injection (DCBEI) is a biopharmaceutical that contains 17 types of amino acids and 5 types of nucleotides. In this study, we found that DCBEI pretreatment reduced L-Glu-dependent neuroexcitation toxicity by maintaining normal mitochondrial function in HT22 cells. DCBEI treatment also reduced the expression of pro-apoptosis proteins and increased the expression of anti-apoptosis proteins. Furthermore, DCBEI attenuated AD-like behaviors (detected via the Morris water maze test) in B6C3-Tg (APPswePSEN1dE9)/Nju double transgenic (APP/PS1) mice; this effect was associated with a reduction in the amount of Aβ and neurofibrillary tangle deposition and the concomitant reduction of phospho-Tau in the hippocampus. Metabonomic profiling revealed that DCBEI regulated the level of neurotransmitters in the hippocampus of APP/PS1 mice. Label-free proteomics revealed that DCBEI regulated the expression of Nrf-2 and its downstream targets, as well as the levels of phospho-protein kinase B and mitogen-activated protein kinase. Together, these data show that DCBEI can ameliorate AD symptoms by upregulating Nrf2-mediated antioxidative pathways and thus preventing mitochondrial apoptosis.