A1R-CT Peptide Disrupts Neurabin Binding for Neuroprotection
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for neurological conditions such as epilepsy and neurodegenerative diseases lack effective anticonvulsant and neuroprotective agents that specifically target the adenosine 1 receptor (A1R) to reduce neuronal excitability and promote neuroprotection.
Innovation Solution
Development of a peptide agent comprising the C-terminal region of the A1R (A1R-CT) that disrupts the binding between A1R and neurabin, thereby enhancing A1R activity and promoting anticonvulsant and neuroprotective effects without affecting other protein functions.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If neurabin binds to A1R, then A1R activity is reduced, but this binding prevents effective anticonvulsant and neuroprotective effects
Solution Approach 1:
The invention extracts the C-terminal region of A1R (amino acids 293-326) as a separate peptide entity (A1R-CT) that can function independently to block the A1R-neurabin interaction. This extracted peptide specifically interrupts the binding between full-length A1R and neurabin, thereby releasing A1R from inhibitory binding while maintaining other A1R functions intact.
Solution Approach 2:
The A1R-CT peptide acts as an intermediary molecule that mediates the disruption of the A1R-neurabin complex. By introducing this intermediate peptide, the invention prevents direct binding between A1R and neurabin, allowing A1R to remain active without the inhibitory effect of neurabin binding, thus achieving anticonvulsant and neuroprotective effects.
2Reliability
If A1R activity is increased to produce anticonvulsant effects, then seizure severity is reduced, but non-specific targeting may affect other protein functions
Solution Approach 1:
The invention applies local quality by using only the C-terminal region (amino acids 293-326) of A1R to create a targeted peptide that specifically blocks the A1R-neurabin interaction site. This localized approach ensures that only the specific binding interface between A1R and neurabin is affected, while other functional regions of A1R remain intact and operational, achieving specificity in its action.
Solution Approach 2:
The invention segments the A1R protein by isolating and utilizing only its C-terminal region (amino acids 293-326) as a functional peptide. This segmentation allows the peptide to perform the specific function of blocking neurabin binding without the complexity and potential side effects of using the full-length protein, thereby enhancing specificity and reducing off-target effects.
Data Source
AI summary
Epileptic seizures cannot be effectively controlled in many patients, thereby necessitating the development of novel therapeutic agents. Activation of the A1 receptor (A1R) by endogenous adenosine is an intrinsic mechanism to self-terminate seizures and protect neurons from excitotoxicity. However, targeting A1R for neurological disorders has been hindered by side effects associated with its broad expression outside the nervous system. Herein, the neural-specific A1R/neurabin/RGS4 complex that dictates A1R signaling strength and response outcome in the brain is targeted. A peptide was developed to block the A1R-neurabin interaction and enhance A1R activity. Anticonvulsant and neuroprotective effects are achieved through enhanced A1R function in response to endogenous adenosine in the brain, thus avoiding side effects associated with A1R activation in peripheral tissues and organs.