NMDA Receptor Blockers Increase 20S Proteasome Activity
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Solution Overview
Problem
Aging is associated with malfunctioning of the protein homeostasis network, leading to protein misfolding and aggregation, which is linked to various human diseases and is difficult to separate from age-associated diseases.
Innovation Solution
The use of NMDA receptor blockers is proposed to increase 20S proteasome activity, thereby enhancing protein degradation and mitigating protein misfolding and aggregation associated with aging and age-related diseases.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Productivity
If NMDA receptor blockers are used to increase 20S proteasome activity, then protein degradation capability is improved, but the complexity of the treatment approach increases
Solution Approach 1:
The invention changes the physiological parameter of NMDA receptor activity through pharmacological intervention. By blocking NMDA receptors with specific antagonists, the system induces a parameter change that cascades to increase 20S proteasome activity, thereby resolving the contradiction between maintaining simple treatment and achieving improved protein degradation
Solution Approach 2:
The NMDA receptor acts as an intermediary target in the therapeutic pathway. Rather than directly targeting the proteasome system, the invention uses NMDA receptor blockers as mediators that indirectly activate 20S proteasome activity through physiological signaling pathways, simplifying the direct intervention while achieving the desired effect
2Reliability
If proteasome activity is increased to clear misfolded proteins, then protein homeostasis is improved, but the risk of off-target effects increases
Solution Approach 1:
The invention extracts and selectively targets only the 20S proteasome pathway by using NMDA receptor blockers that specifically induce activation of this pathway. This selective extraction of the desired proteolytic function minimizes interference with other cellular processes, thereby reducing off-target effects while maintaining reliable proteostasis
Solution Approach 2:
The therapeutic mechanism incorporates physiological feedback control where NMDA receptor blockade triggers a cascade that increases 20S proteasome activity only when needed for clearing misfolded proteins. This feedback-regulated activation ensures reliable proteostasis maintenance while avoiding constitutive activation that could lead to off-target effects
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
Increasing 20S proteasome activity with NMDA receptor blockers effectively treats and prevents proteinopathies by reducing the accumulation of oxidatively damaged and misfolded proteins, thereby delaying aging and associated diseases.
Implementation Method 1
NMDA receptor blockers increase the activity of 20S proteasomes, which are responsible for the degradation of oxidatively damaged proteins
Implementation Method 2
The oxidative stress is another factor that cause protein unfolding. Upon oxidative damage, proteins unfold and expose hydrophobic regions which makes them prone to aggregation
Data Source
AI summary
The usage of NMDAR antagonists provides compositions and methods for treatment for the malfunctioning of the protein homeostasis network and interferes with crucial signaling pathways and is often associated with multiple human diseases. Importantly, the present invention provides informations comprising at least one NMDA receptor blockers for use in preventing and/or treating ageing and ageing associated conditions and diseases through increasing 20S proteasome activity.