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Application of PGC-1Alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) in preparation of medicines for treating vascular dementia

A technology of vascular dementia and PGC-1, applied in the field of biochemistry, can solve the problems of insignificant curative effect and unspecific targeting of vascular dementia, and achieve the effect of inhibiting neuroinflammation in the hippocampus and reducing the production of ROS

Active Publication Date: 2017-07-14
GENERAL HOSPITAL OF TIANJIN MEDICAL UNIV
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

[0005] In order to solve the problem that the existing medicines for treating vascular dementia have no exact pertinence and the curative effect is not significant, the proposed application of PGC-1α in the preparation of medicines for treating vascular dementia

Method used

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  • Application of PGC-1Alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) in preparation of medicines for treating vascular dementia
  • Application of PGC-1Alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) in preparation of medicines for treating vascular dementia
  • Application of PGC-1Alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) in preparation of medicines for treating vascular dementia

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Experimental program
Comparison scheme
Effect test

Embodiment 1

[0019] Example 1 The learning and memory ability of mice with chronic cerebral ischemia is impaired, the expression of PGC-1α in the hippocampus is reduced, and the mRNA of antioxidants is also reduced

[0020] Wild-type C57BL / 6J mice were induced to form chronic cerebral hypoperfusion by bilateral common carotid artery stenosis (BCAS), and the vascular dementia model was successfully established and confirmed.

[0021] figure 1 A: The mice in the experimental group and the sham operation group learned in the water maze. With the increase of the test days, the average escape time of the mice in the operation group was significantly higher than that in the sham operation group, indicating that the spatial learning ability of the mice in the experimental group was significantly impaired. figure 1 B: qRT-PCR analysis showed that the expression levels of mitochondrial antioxidant mRNA (SOD2, Prx3, Trx2, GPx) in the hippocampus were significantly down-regulated in the operation gro...

Embodiment 2

[0023] Example 2 Overexpression of PGC-1α in neurons can alleviate cognitive dysfunction caused by chronic cerebral hypoperfusion

[0024] To assess mouse performance in the water maze, the LTP assay measures hippocampal synaptic plasticity. To examine the effectiveness of PGC-1α overexpression, the expression of PGC-1α protein was quantified by Western blot experiments. In addition, the expression of IRES-eGFP neurons was observed in frozen sections of brain tissue observed under a fluorescent microscope, indicating the presence of PGC-1α in neurons ( figure 2 A). Test the performance of PGC-1α overexpressed mice in the water maze experiment to determine whether the specific neuron overexpression of PGC-1α is related to the ability of spatial learning and memory. Sham operation group, PGC-1α f / f +BCAS group, PGC-1α f / f A typical swimming route of Eno2-Cre+BCAS mice is shown in figure 2 b. figure 2 C shows that PGC-1α f / f +BCAS group and PGC-1α f / f Compared with ...

Embodiment 3

[0027] Example 3 PGC-1α prevents nerve damage in chronic cerebral hypoperfusion

[0028] Immunohistochemical and Western blot analysis revealed: PGC-1α f / f +BCAS group compared with sham operation group mice, PGC-1α f / f The expression of brain-derived neurotrophic factor BDNF in the hippocampus of mice in +BCAS group was significantly reduced (pf / f Eno2-Cre+BCAS group mice and PGC-1α f / fCompared with mice in +BCAS group, the expression of brain-derived neurotrophic factor was significantly enhanced (p image 3 A-C, image 3 A and B are BDNF images of immunohistochemical staining of brain tissue sections (magnified 200 times); image 3 C is Western blot detection of brain-derived neurotrophic factor). The experimental results showed that overexpression of PGC-1α increased the expression of brain-derived neurotrophic factor BDNF. The number of hippocampal neurons also appeared to be affected by PGC-1α overexpression. Compared with the sham group, PGC-1α f / f The number o...

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Abstract

The invention discloses an application of PGC-1Alpha (peroxisome proliferator-activated receptor-gamma coactivator-1alpha) in the preparation of medicines for treating vascular dementia. The overexpression of PGC-1Alpha can simultaneously induce the expression of brain-derived neurotrophic factor, enhance the expression of cholinergic system molecules, increase the expression of mitochondrial antioxidant and uncoupling protein expression, reduce the production of ROS (reactive oxygen species) and inhibit the neuroinflammation of the hippocampus. The invention links various research mechanisms together, providing a new direction for the development of specific medicines for treating vascular dementia, so a broad application prospect is realized.

Description

technical field [0001] The invention relates to the field of biochemistry, in particular to the use of PGC-1α protein in the preparation of drugs for treating vascular dementia. Background technique [0002] Vascular dementia is cognitive impairment caused by ischemic or hemorrhagic cerebrovascular disease, global cerebral ischemia and hypoxia, mainly memory and cognitive impairment, and may be accompanied by language, movement, visual-spatial skills and personality disorders Wait. Vascular dementia has become one of the main factors of mental and physical disability in our country. As the population ages, its incidence is increasing. Vascular dementia seriously affects the social adaptability, living ability and physical and mental health of the elderly, and brings a heavy burden to the society and family members. [0003] Due to the unclear pathogenesis of vascular dementia, there is currently no effective treatment. Current studies have shown that the pathogenesis of ...

Claims

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Application Information

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IPC IPC(8): A61K38/17A61P25/28
CPCA61K38/1709
Inventor 郝峻巍韩滨卜亚丽
Owner GENERAL HOSPITAL OF TIANJIN MEDICAL UNIV
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