Application of combination of natural immune agonist and brain homeostasis regulatory protein in treating Alzheimer's disease
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A technology of natural immunity and protein regulation, applied in the field of biomedicine, can solve the problem that the pathological process of TREM2AD is not very clear
Pending Publication Date: 2020-02-07
LIAOCHENG CITY ORIENT BIOMEDICAL TECH CO LTD
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Embodiment 1
[0024] Example 1: Preparation of STING agonist
[0025] Preparation of cGAMP: cGAMP (cyclized-GMP-AMP) was catalyzed and synthesized by cyclized cGMP-AMP dinucleotide synthetase (cGAS) according to the literature method under activation conditions after binding to DNA. The purity is above 98%. (Pingwei Li, et al., Immunity, 2013, 39(6), 1019-1031.). Thio-cGAMP, c-di-AMP, thio-c-di-AMP, c-di-GMP were purchased from sigma company.
Embodiment 2
[0026] Example 2: Brain Homeostasis Regulation Protein Zn 7 Preparation of MT3gH625
[0027] All biochemical reagents and kits were purchased from Sigama or Invitrogen unless otherwise specified. Zn 7 The preparation of MT3gH625 was carried out according to the literature method. (Wei Xu, Qiming Xu, Hao Cheng, Xiangshi Tan, Scientific reports, 2017, 7(1), 13763.)
[0028] Zn 7 Determination of metal content in MT3gH625
[0029] Take a certain amount of recombined fusion protein Zn 7 MT3gH625 was nitrified overnight at 65°C with a small amount of concentrated nitric acid, diluted 10 times, and the content of metal Zn was measured on an inductively coupled plasma optical emission spectrometer (ICP-OES). The results show that each mole of Zn after recombination 7 The MT3gH625 fusion protein contained 7±0.2 moles of Zn.
[0030] Zn 7 Removal of endotoxin in MT3gH625
[0031] Zn 7 MT3gH625 first uses ultrafiltration membrane to intercept aggregated endotoxin (LPS), and t...
Embodiment 3
[0032] Example 3: Alzheimer's disease mouse model and STING agonist combined with Zn 7 MT3gH625 drug treatment APP / PS1 transgenic mice were purchased from Beijing Zhongke Zesheng Biotechnology Co., Ltd., 4 months old, weighing 24-26g. Test drug name: STING agonist, STING agonist combined with Zn 7 MT3gH625. Properties: white powder. Vehicle: normal saline. Preparation method: Prepare the solution with the required concentration with physiological saline solution before use. The dosage is: 10mg / kg. Administration method: intraperitoneal injection; administration frequency: once a day for 60 consecutive days.
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Abstract
The invention belongs to the technical field of medicines, and particularly relates to application of a combination of natural immune agonist and brain homeostasis regulatory protein in treating Alzheimer's disease. The brain homeostasis balance regulatory protein can pass through a blood brain barrier, so that homeostasis balance of brain metal ions is effectively regulated and controlled, homeostasis balance of active oxygen species is effectively inhibited, and toxic senile plaques are effectively reduced. The natural immune agonist can effectively regulate brain immune cell functions and reduce pathological features such as chronic brain inflammation. The combination of the brain homeostasis regulatory protein and the natural immune agonist can significantly improve the nerve cell morphology of hippocampus, inhibit nerve cell apoptosis, eliminate toxic amyloid deposition, improve the learning and memory ability of model mice, and prevent the development of Alzheimer's disease. Therefore, the combination of the brain homeostasis regulatory protein and the natural immune agonist has a wide application prospect in the aspect of treating Alzheimer's disease.
Description
technical field [0001] The invention belongs to the technical field of biomedicine, and specifically relates to the application of a natural immune regulator combined with a brain homeostasis regulatory protein in the treatment of Alzheimer's disease. The use of brain homeostasis regulatory proteins combined with natural immune regulators can significantly improve the morphology of neurons in the hippocampus and inhibit the apoptosis of neurons, improve the learning and memory ability of the brain, inhibit amyloid deposition and chronic inflammation of the brain, and prevent the development of Alzheimer's disease. Background technique [0002] Alzheimer's Disease (AD), commonly known as senile dementia, has become one of the most serious diseases in the world. There are few anti-Alzheimer's disease drugs approved by the US FDA and China CFDA, and the drugs treat the symptoms but not the root cause. The curative effect is not significant. Most of the global anti-Alzheimer's ...
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