Unlock instant, AI-driven research and patent intelligence for your innovation.

Methods of preventing and/or treating cognitive impairment and neuroinflammation associated with aging

A technology for cognitive impairment and aging, applied in the field of 2-[4-phenyl]-1H-benzimidazole, which can solve the problems that the role of microglial cells has not yet been reported

Active Publication Date: 2022-01-04
THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV
View PDF8 Cites 0 Cited by
  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

However, the role of intrinsic regulatory pathways in microglia in these phenomena has not been reported

Method used

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
View more

Image

Smart Image Click on the blue labels to locate them in the text.
Viewing Examples
Smart Image
  • Methods of preventing and/or treating cognitive impairment and neuroinflammation associated with aging
  • Methods of preventing and/or treating cognitive impairment and neuroinflammation associated with aging
  • Methods of preventing and/or treating cognitive impairment and neuroinflammation associated with aging

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0038] Example 1. Ppargc1a activator ZLN005 inhibits metabolic dysfunction of microglial cells in aged mice

[0039] Aged animals were treated orally with 0.5% methylcellulose (vehicle) or 25 mg / kg ZLN005 (Sigma) (in vehicle) 3 times a week for 15 weeks, starting at 37 weeks of age. Treated old animals (n=6), untreated old animals (n=6) and young animals (20 weeks old, n=6) were sacrificed after drug treatment and their brain tissues were collected. Brain tissues of sacrificed animals perfused with PBS were digested with collagenase I and analyzed by flow cytometry (Ginhoux et al. "Science" 330:841-5, 2010). Brain microglial cells were treated with 2-NBDG (2-(N-(7-nitrobenzo-2-oxa-1,2-oxadiazol-4-yl)amino)-2-deoxyglucose, Invitrogen ) and anti-Slc2a1 antibody (RnD) for flow cytometry harvesting (LSRII, BD) and analysis (FlowJo).

[0040] The results are summarized in figure 1 Middle; Y-axis represents % of microglia expressing the glucose transporter Slc2a1 or having taken...

Embodiment 2

[0041] Example 2. Ppargc1a activator ZLN005 inhibits the production of inflammatory cytokines in aged mouse microglial cells

[0042] Aged animals were treated orally with 0.5% methylcellulose (vehicle) or 25 mg / kg ZLN005 (Sigma) (in vehicle) 3 times a week for 15 weeks, starting at 37 weeks of age. Treated old animals (n=6), untreated old animals or senescent animals (n=6) and young animals (20 weeks old, n=6) were sacrificed after drug treatment and their brains were collected organize. Brain tissues of sacrificed animals perfused with PBS were digested with collagenase I and analyzed by flow cytometry (Ginhoux et al. "Science" 330:841-5, 2010). Brain microglia were phenotyped with fluorochrome-labeled CCL2 antibody and TNF-α (Biolegend) for flow cytometric harvest (LSRII, BD) and analysis (FlowJo).

[0043] The results are summarized in figure 2 Middle; Y-axis represents % of microglia expressing CCL2 or TNF-α. Statistical analysis was performed by ANOVA. The results ...

Embodiment 3

[0044] Example 3. Ppargc1a activator ZLN005 inhibits systemic inflammation in aged mice

[0045] Serum TNF-α levels in young mice, vehicle-treated aged mice, and ZLN-treated aged mice (from Example 2) were measured by ELISA to determine TNF-α levels indicative of systemic inflammation. The results are summarized in Table 3; the Y-axis represents the concentration of serum TNF-α. The results showed that by administering ZLN005 to aged animals, serum TNF-α levels in these treated and aged animals were reduced compared to vehicle-treated aged animals, thereby suppressing systemic inflammation (p-value<0.05). Statistical analysis was performed using an unpaired t-test.

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

PUM

No PUM Login to View More

Abstract

The present invention relates to methods for preventing and / or treating cognitive impairment of the central nervous system associated with aging. The method comprises administering to a subject in need thereof an effective amount of the Ppargc 1a activator 2-(4-tert-butylphenyl)-1H-benzimidazole, 2-[4-(1,1-dimethyl (ethyl)phenyl]-1H-benzimidazole. The preferred route of administration is oral administration.

Description

technical field [0001] The present invention relates to a method of preventing and / or treating cognitive impairment and neuroinflammation associated with aging by administering to a subject the Ppargc 1a activator 2-(4-tert-butylphenyl)-1H-benzo Imidazole, namely 2-[4-(1,1-dimethylethyl)phenyl]-1H-benzimidazole. Background technique [0002] Microglia are immune cells located exclusively in the CNS. Microglial cells originate from the yolk sac hematopoietic progenitor and populate the brain during embryogenesis (Ginhoux et al., Science 2009). During homeostatic conditions, microglia perform repair processes such as the removal of debris. They also produce an "arsenal" of inflammatory mediators that are released upon pathological stimuli to initiate and maintain neuroinflammation. Similar to other immune cells, the activation of microglia is a process with bioenergetic demands. What remains elusive is how the metabolism of microglia becomes adaptive and contributes to the...

Claims

the structure of the environmentally friendly knitted fabric provided by the present invention; figure 2 Flow chart of the yarn wrapping machine for environmentally friendly knitted fabrics and storage devices; image 3 Is the parameter map of the yarn covering machine
Login to View More

Application Information

Patent Timeline
no application Login to View More
Patent Type & Authority Patents(China)
IPC IPC(8): C07D235/18A61K31/41C07D401/04
CPCC07D235/18A61K31/4184A61P25/00A61P29/00A61K31/404C07D401/04A61K9/0053
Inventor K·D·恩古彦E·G·英格利曼
Owner THE BOARD OF TRUSTEES OF THE LELAND STANFORD JUNIOR UNIV