Polypeptide Salts Inhibit PSD-95 NMDA Receptor Interaction
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Solution Overview
Problem
Current therapeutic options for ischemic stroke and other nervous system disorders, such as Alzheimer's and epilepsy, often come with significant side effects and insufficient therapeutic efficiency, highlighting the need for more effective treatments that target excitatory neurotoxicity pathways.
Innovation Solution
Development of pharmaceutically acceptable salts of polypeptides, specifically those with the amino acid sequence YEKLLDTEI or functional variants, which inhibit the interaction between NMDA receptors and postsynaptic density 95 protein (PSD-95), potentially used as neuroprotective agents to treat or prevent nervous system injuries and disorders.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If conventional therapeutic drugs (vasodilators, thrombolytic drugs, anticoagulant drugs) are used for ischemic stroke, then blood flow improvement and clot dissolution are achieved, but significant side effects and potential risks occur
Solution Approach 1:
The patent introduces a polypeptide compound as an intermediary substance that blocks the interaction between PSD-95 and NMDA receptors. This mediator prevents excitatory neurotoxicity without causing the systemic side effects of conventional drugs like vasodilators and thrombolytic agents, thereby improving therapeutic safety while reducing harmful effects.
Solution Approach 2:
The invention extracts and targets the specific pathological mechanism of excitatory neurotoxicity mediated by PSD-95-NMDA interaction. By isolating this specific pathway for therapeutic intervention, the patent avoids the broad-spectrum effects of conventional drugs that cause significant side effects, achieving selective neuroprotection.
2Reliability
If conventional therapeutic drugs are used for ischemic stroke, then some therapeutic effect is achieved, but therapeutic efficiency is insufficient
Solution Approach 1:
The patent employs preliminary neuroprotective action by blocking the PSD-95-NMDA interaction pathway before excitatory neurotoxicity can fully develop. This preventive approach preserves neuronal function and improves therapeutic efficiency by addressing the root mechanism rather than merely treating symptoms after damage occurs.
Solution Approach 2:
The invention changes the therapeutic parameter from general hemodynamic management (vasodilation, thrombolysis) to specific molecular pathway modulation (PSD-95-NMDA interaction blockade). This parameter change enables more efficient and targeted therapy with better clinical outcomes.
3Quantity of substance
If NMDA receptor activation occurs in response to excitatory neurotransmitters, then ion channel opening and calcium ion influx occur, but neuronal cell damage is triggered through multiple pathways
Solution Approach 1:
The patent converts the harmful overactivation of NMDA receptors into a beneficial therapeutic target. By designing a polypeptide that specifically blocks the pathological PSD-95-NMDA interaction while preserving normal neuronal function, the invention transforms the harmful calcium influx pathway into a controllable therapeutic mechanism that prevents neuronal damage.
Solution Approach 2:
The polypeptide compound acts as an intermediary that modulates the PSD-95-NMDA interaction. It prevents excessive calcium ion influx and subsequent neuronal damage without completely blocking NMDA receptor function, thereby converting a potentially harmful process into a controlled physiological state.
Data Source
AI summary
There is provided in the present application a pharmaceutically acceptable salt of a polypeptide and a pharmaceutical composition comprising the same, wherein the polypeptide comprises the amino acid sequence YEKLLDTEI (SEQ ID NO:1) or a functional variant thereof.