Application of alfuzosin compound in prevention or treatment of Alzheimer's disease and related diseases

A technology of alfuzosin and compounds, applied in the application field of alfuzosin compounds in the prevention or treatment of Alzheimer's disease and related diseases, which can solve the problems of limited intervention strategies, no vascular aging, etc., and achieve degradation pathology Accumulation of sexual protein, improvement of vascular endothelial cell function, improvement of mitochondrial metabolism

Pending Publication Date: 2020-04-21
北京安塞迩生物科技有限公司
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, clinically, the intervention strategies for inhibiting vascular aging and improving vascular function are extremely limited. In addition to improving environmental factors such as increasing exercise and controlling diet, drug treatment only has indirect strategies such as lowering blood sugar and blood lipid drugs. Drugs for vascular aging are used clinically [Abdelkarim D (2019) A neural-vascular complex of age-related changes in the human brain: Anatomy, physiology, and implications for neurocognitive aging Neurosci Biohehav Rev 107: 927-44; Lin CH (2018) VascularAging and Cognitive Dysfunction: Silent Midlife Crisis in the Brain Pulse 5:127-32]

Method used

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  • Application of alfuzosin compound in prevention or treatment of Alzheimer's disease and related diseases
  • Application of alfuzosin compound in prevention or treatment of Alzheimer's disease and related diseases
  • Application of alfuzosin compound in prevention or treatment of Alzheimer's disease and related diseases

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0069] Embodiment 1: Alfuzosin has the effect of degrading APP protein

[0070] like figure 1 and figure 2 As shown, the fusion protein of amyloid precursor protein (APP) and GFP (APP-GFP) was overexpressed in Hek293T cells. After expressing APP-GFP, alfuzosin was added to the cell culture medium (AZ 1 μM or 10 μM 24 hours later, GFP immunostaining was performed). The fluorescence intensity of GFP in the non-administration group was set as 1, and the relative fluorescence intensity of the AZ treatment group was represented by a histogram. Mean±standard error (mean±SE) repeated 5 times (N=5). White histograms represent the control group. After one-way ANOVA statistical analysis, the experimental groups with p<0.05 are represented by black histograms. This result shows that alfuzosin has the effect of reducing amyloid precursor protein.

Embodiment 2

[0071] Example 2: Alfuzosin and its derivative compounds have the effect of degrading APP protein

[0072] like image 3 and Figure 4As shown, the fusion protein of amyloid precursor protein (APP) and GFP (APP-GFP) was overexpressed in Hek293T cells. After expressing APP-GFP, different doses of alfuzosin (AZ1 μM, 10 μM or 100 μM), TZ-md, AZ-md and other α1 receptor blockers were added to the cell culture medium: including tamsulosin (Tamsulosin or Tam), Silodosin (Silodosin or Sil). The immunoblotting intensity of APP-GFP in the non-administered group was set as 1, and the relative intensity of the AZ-treated group was represented by a histogram. Mean±standard error (mean±SE) repeated 5 times (N=5). White histograms represent the control group. After one-way ANOVA statistical analysis, the experimental groups with p<0.05 are represented by black histograms. Experimental groups not statistically significant are represented by gray histograms. This result shows that AZ, ...

Embodiment 3

[0073] Example 3: Alfuzosin and its derivative compounds have the effect of increasing intracellular ATP levels

[0074] like Figure 5 As indicated, in the human neuroblastoma BE(2)-M17 cell line, cellular ATP changes were examined after 24 hours of treatment with different compounds. The ATP content of the non-administered group was set as 1, and the relative ATP content of the drug-treated group was represented by a histogram. Mean±standard error (mean±SE) repeated 6 times (N=6). White histograms represent the control group. After one-way ANOVA statistical analysis, the experimental groups with p<0.05 are represented by black histograms. Experimental groups not statistically significant are represented by gray histograms. This result indicated that AZ, TZ-md and AZ-md could increase the intracellular ATP level. Whereas increasing ATP degrades non-specific protein aggregation, explains the results of Examples 1 and 2 and is consistent with the results presented below. ...

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Abstract

The invention relates to an application of an alfuzosin compound in prevention or treatment of Alzheimer's disease and related diseases, and belongs to the technical field of medicines. The alfuzosincompound has the effects of improving mitochondrial metabolism, degrading accumulation of various pathological proteins and improving vascular endothelial cell functions. The invention provides a newpharmaceutical application of the alfuzosin compound. The new pharmaceutical application can provide a new choice for treatment of clinical related diseases. Alfuzosin, an alfuzosin isomers, TZ-md andAZ-md can be beneficially applied to Alzheimer's disease and related complications, such as seeing and hearing impairment, anemia, blood pressure instability, insomnia, depression, limb dysfunction,malnutrition, weakness, dizziness, gait instability and the like, and diseases related to protein accumulation and metabolic disorder, such as Huntington's disease, amyotrophic lateral sclerosis, dementia with Lewis bodies, multi-system atrophy and the like.

Description

technical field [0001] The invention belongs to the technical field of medicine, and in particular relates to the application of alfuzosin compounds in the prevention or treatment of Alzheimer's disease and related diseases. Background technique [0002] Alzheimer's Disease (or AD) is a dementia caused by a chronic progressive central nervous system degenerative disease. Alzheimer's disease is characterized by neuropsychiatric symptoms such as progressive memory impairment, cognitive dysfunction, personality changes, and language impairment. Common complications of Alzheimer's disease include visual and hearing impairment, anemia, unstable blood pressure, depression, insomnia, limb dysfunction, malnutrition, weakness, dizziness, and unsteady gait. Alzheimer's disease often starts in old age or pre-senile age, and usually develops slowly and gradually progresses, with dementia as the main manifestation. Patients with a family history of the same disease develop faster. Abou...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): A61K31/517A61P25/28A61P25/20A61P25/24A61P19/00A61P3/02A61P39/00A61P1/08
CPCA61K31/517A61P25/28A61P25/20A61P25/24A61P19/00A61P3/02A61P39/00A61P1/08
Inventor 刘磊韦西蒙
Owner 北京安塞迩生物科技有限公司
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