L-PGDS Production Promotion in Pericytes Using Vaccinia Tissue Extract
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Solution Overview
Problem
There is a lack of substances that effectively promote lipocalin-type prostaglandin D2 synthase (L-PGDS) production, which is crucial for brain-protective and sleep-promoting actions, and no effective screening methods for drugs targeting L-PGDS associated diseases such as cerebral infarction and Alzheimer's disease.
Innovation Solution
An extract from inflamed tissues of animals inoculated with vaccinia virus is used to promote L-PGDS production in ischemia-induced multipotent stem cells (iSCs), serving as an index for screening drugs with brain-protective and sleep-promoting actions, and is developed into a highly safe pharmaceutical preparation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Quantity of substance
If conventional methods are used to promote L-PGDS production, then L-PGDS levels increase, but no effective substances or screening methods exist currently
Solution Approach 1:
The patent uses vaccinia virus as an intermediary substance to stimulate L-PGDS production. The virus infects animal tissues, triggering an immune response that upregulates L-PGDS expression. This mediator approach solves the problem of finding effective promoting substances by using a biological agent that naturally induces L-PGDS synthesis through immune activation.
Solution Approach 2:
The patent changes the biological state parameters of animal tissues by introducing vaccinia virus infection, which alters the expression levels of L-PGDS. By modifying the physiological condition (from healthy to virus-infected state), the system naturally increases L-PGDS production without requiring direct chemical intervention.
2Reliability
If L-PGDS production is increased, then brain-protective and sleep-promoting actions are enhanced, but screening methods for such drugs are lacking
Solution Approach 1:
The patent establishes a feedback-based screening system where L-PGDS production levels serve as a measurable indicator of drug efficacy. By using L-PGDS expression as a feedback signal, researchers can screen and evaluate compounds that promote L-PGDS production, thereby identifying drugs with brain-protective and sleep-promoting actions through a quantifiable metric.
Solution Approach 2:
The patent replaces complex functional assays for measuring brain protection and sleep promotion with a more straightforward molecular biology approach - measuring L-PGDS protein or mRNA levels. This substitution simplifies the screening process by using accessible molecular markers instead of requiring complex behavioral or physiological measurements.
3Productivity
If L-PGDS is used as a carrier for lipophilic molecules, then transport function is enhanced, but specificity of target delivery is reduced
Solution Approach 1:
The patent exploits the natural local quality of L-PGDS by targeting its overexpression to specific brain regions affected by disease. Rather than attempting to control where the carrier delivers molecules systemically, the approach uses localized upregulation of L-PGDS in diseased areas to create region-specific transport capacity, thereby maintaining target delivery specificity through spatial concentration of the carrier protein.
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 extract increases L-PGDS production, reducing Aβ levels and improving cognitive function in Alzheimer's disease models, providing a therapeutic and preventive agent for cerebrovascular disorders and dementia, with minimal side effects.
Implementation Method 1
L-PGDS has a catalytic activity for isomerization of prostaglandin H2 (PGH2), which is a common intermediate reaction in prostaglandin biosynthesis, to prostaglandin D2 (PGD2)
Implementation Method 2
L-PGDS has a huge lipophilic pocket as compared to other lipocalins. Thus, it is thought that L-PGDS acts as a transporter protein and a scavenger for various lipophilic molecules in the brain
Implementation Method 3
when subarachnoid hemorrhage occurs, an intracerebral L-PGDS level is increased, and protects brain from neuronal damages by conjugating with bilirubin, a neurotoxic substance
Implementation Method 4
L-PGDS strictly binds to a site essential for oligomerization of amyloid β-protein (Aβ, a senile plaque) to inhibit formation of Aβ deposition in cerebrospinal fluid and cytotoxicity
Data Source
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AI summary
An object of the present invention is to provide a lipocalin-type prostaglandin D2 synthase (L-PGDS) production promoting agent, more specifically an L-PGDS production promoting agent in pericytes or ischemia-induced multipotent stem cells (iSCs) dedifferentiated from pericytes. In the present invention, it has been found that a substance having an L-PGDS production promoting action is contained in an extract from inflamed tissues inoculated with vaccinia virus. An L-PGDS production promoting agent is highly useful as a preventive, therapeutic or relapse preventive agent for a disease in which the effect by promotion of L-PGDS expression is expected to be effective, including a cerebrovascular disorder such as cerebral infarction, dementia such as Alzheimer's disease, or a sleep disorder.