HPYD Peptide Inhibits Aβ Aggregation via β-Sheet Breaker Mechanism
Find Innovative SolutionsGenerate Solutions
Solution Overview
Problem
Current treatments for Alzheimer's disease fail to effectively target and inhibit the essential β-sheet formation in Aβ aggregation, leading to ongoing neurotoxicity and plaque formation in the brain.
Innovation Solution
A polypeptide with the sequence His-Lys-Gln-Leu-Pro-Phe-Tyr-Glu-Asp (HPYD) specifically binds to β-amyloid protein monomer Aβ1-42, stabilizing its normal spatial structure, preventing β-sheet formation, and inhibiting the aggregation of Aβ peptides, thereby reducing the formation of soluble oligomers and plaques.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments are used for Alzheimer's disease, then general symptom management is achieved, but the essential β-sheet formation in Aβ aggregation is not effectively inhibited
Solution Approach 1:
The patent introduces a β-sheet breaker peptide as an intermediary substance that mediates between the Aβ peptides and prevents their harmful aggregation. The peptide acts as a molecular mediator that interferes with the β-sheet formation process, thereby blocking the pathway from Aβ monomers to toxic oligomers and plaques without directly removing or degrading the Aβ peptides themselves.
Solution Approach 2:
The invention extracts and isolates the critical β-sheet structural element from the Aβ aggregation process and targets it specifically. By designing a peptide that selectively binds to and stabilizes the non-aggregated form of Aβ, the treatment extracts the harmful β-sheet conformational change from the aggregation pathway, preventing it from occurring while leaving the Aβ peptide itself intact for potential clearance mechanisms.
2Productivity
If β-sheet abundant structures are formed in Aβ, then aggregation occurs more quickly, but this leads to increased neurotoxicity and plaque formation
Solution Approach 1:
The β-sheet breaker peptide performs preliminary anti-action by preemptively binding to Aβ monomers and preventing the conformational change to β-sheet structures before aggregation can occur. This preliminary intervention blocks the formation of the toxic oligomeric intermediates that would otherwise form rapidly through β-sheet stacking, thereby preventing neurotoxicity before it can develop.
Solution Approach 2:
The invention changes the structural parameters of Aβ by inducing and stabilizing alternative conformations that lack the β-sheet rich structure necessary for rapid aggregation. The peptide modifies the secondary structure parameters of Aβ, shifting the equilibrium from aggregated β-sheet forms to soluble, non-toxic conformations with different structural characteristics.
3Quantity of substance
If Aβ soluble oligomers are formed, then neurological functions are affected, but the density of plaque deposition is less relevant to cognitive impairment
Solution Approach 1:
The β-sheet breaker peptide performs preliminary action by preventing the formation of soluble oligomers in the first place. By stabilizing Aβ monomers in non-aggregated conformations before they can oligomerize, the treatment stops the pathological process at the monomeric stage, preventing the formation of the toxic soluble oligomers that directly impair neurological functions.
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
HPYD effectively inhibits Aβ aggregation and plaque formation, promoting the degradation and removal of Aβ peptides, offering a promising approach for the prevention and treatment of Alzheimer's disease by reducing neurotoxicity and improving cognitive functions.
Implementation Method 1
A polypeptide with the sequence His-Lys-Gln-Leu-Pro-Phe-Tyr-Glu-Asp (HPYD) specifically binds to β-amyloid protein monomer Aβ1-42, stabilizing its normal spatial structure
Implementation Method 2
stabilizing its normal spatial structure, preventing β-sheet formation
Implementation Method 3
inhibiting the aggregation of Aβ peptides, thereby reducing the formation of soluble oligomers and plaques
Data Source
AI summary
Provided in the present invention are a β-sheet breaker peptide used for preventing and/or treating Alzheimer's disease, and the use thereof for preventing and/or treating Alzheimer's disease. The amino acid sequence of the β-sheet breaker peptide is His-Lys-Gln-Leu-Pro-Phe-Tyr-Glu-Glu-Asp (SEQ ID NO:1). The polypeptide can specially bind to a β-amyloid protein monomer (Aβ1-42), and prevent the formation of β-sheet, thereby inhibiting Aβ peptide aggregation, reducing the formation of Aβ soluble oligomer, Aβ fiber and senile plaques in the brain, and accelerating the degradation and removal of Aβ peptide.