Odorant Receptor Markers for Microglia Detection and Meningitis Treatment
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Solution Overview
Problem
There is a lack of studies on using odorant receptors (ORs) as markers for microglia and their interaction with pathogen-derived metabolites, particularly for treating bacterial meningitis.
Innovation Solution
A composition and method for detecting microglia using agents that measure the activity or expression level of Olfr110 or Olfr111, and using inhibitors or activators to modulate the interaction between 2-pentylfuran (2-PF) and these odorant receptors for preventing or treating meningitis.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Measurement precision
If conventional markers are used to detect microglia, then the detection method is established, but the ability to detect microglia activity in the context of pathogen-brain axis remains insufficient
Solution Approach 1:
The patent applies universality by demonstrating that odorant receptors (ORs) serve dual functions: they are both olfactory sensors and microglia-specific markers. This allows the same molecular target to enable both odor detection and microglia identification, expanding the detection scope without requiring separate specialized markers for different functions.
Solution Approach 2:
The patent uses odorant receptors as an intermediary marker to bridge the gap between conventional microglia markers and pathogen-brain axis research. By detecting OR expression in microglia, the study can infer microglial activation states in the context of pathogen infection, providing a new mediator for understanding microglia-function in neuroinflammation.
2Loss of information
If the interaction between pathogen-derived metabolites and microglia is studied, then the pathogen-brain axis is illuminated, but the involvement of specific GPCRs remains unclear
Solution Approach 1:
The patent applies parameter changes by systematically investigating different odorant receptor subtypes and their specific ligand preferences. By varying the receptor type (e.g., Olfr110, Olfr111) and measuring their response to different metabolites, the study identifies specific GPCR-ligand interactions that mediate pathogen-brain axis communication, transforming general observations into specific mechanistic insights.
Solution Approach 2:
The patent segments the GPCR family into specific odorant receptor subtypes (Olfr110, Olfr111) and studies each independently for their specific ligand binding characteristics. This segmentation allows precise identification of which receptor-subtype interacts with which pathogen-derived metabolite, providing reliable confirmation of specific GPCR involvement rather than treating all GPCRs uniformly.
3Measurement precision
If odorant receptors are used as microglia markers, then microglia detection is enhanced, but the complexity of identifying specific receptor subtypes increases
Solution Approach 1:
The patent applies local quality by focusing detection on specific odorant receptor subtypes (Olfr110, Olfr111) that are locally expressed in microglia rather than attempting to detect all odorant receptors uniformly. This targeted approach maintains high marker specificity for microglia while simplifying the identification process by concentrating on a limited set of relevant receptor subtypes rather than the entire OR family.
Applied Scientific Principles
This section explains which scientific principles are used to turn an abstract innovation direction into a practical engineering solution.
Function Achieved in This Case
The proposed solution enables effective detection of microglia and modulation of their activity through the interaction with 2-PF and Olfr110 or Olfr111, potentially leading to improved treatments for neuroinflammatory diseases and meningitis.
Implementation Method 1
Microglia expresses various G protein-coupled receptors (GPCRs) biologically detecting large or small molecules (Hickman et al., 2013; McHugh, 2012). Moreover, GPCRs include cytokine receptors and PRRs, which detect small metabolites and affect microglial activation.
Implementation Method 2
They can detect small molecules in various non-olfactory tissues such as renal, dermal and pancreatic tissues (Kang et al., 2015; Kang and Koo, 2012; Massberg and Hatt, 2018). For example, the recognition of a sandalwood scent by OR2AT4 promotes the proliferation of keratinocytes in human skin
Implementation Method 3
using inhibitors or activators to modulate the interaction between 2-pentylfuran (2-PF) and these odorant receptors for preventing or treating meningitis
Data Source
AI summary
Provided are an odorant receptor marker of microglia and a use thereof, and according to the odorant receptor marker of microglia and a use thereof according to one aspect, microglia may be detected by measuring an activity or expression level of a protein of an odorant receptor (OR) Olfr110 or Olfr111, and OR ligands of microglia may be selected using them, and an inhibitor or activator against the interaction between the OR and 2-pentylfuran is effectively used in treatment of a neuroinflammatory disease or meningitis.