Zn2+-Binding Peptide Disaggregates PolyQ Proteins
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Solution Overview
Problem
Current treatments for neurodegenerative diseases caused by protein aggregation, such as Huntington's disease, are either ineffective or have side effects due to affecting healthy protein expression, and there is a need for a drug that specifically targets pathological proteins without impacting healthy counterparts.
Innovation Solution
A plant-derived protein with antiaggregating and disaggregating activity, specifically a Zn2+-binding region-containing protein, is developed to target and reduce the aggregation of extended polyQ stretch proteins, which are associated with neurodegenerative diseases, without affecting healthy protein expression.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If current treatments for neurodegenerative diseases are used, then some therapeutic effect is achieved, but healthy protein expression is affected causing side effects
Solution Approach 1:
The patent applies local quality by designing a peptide with a specific conserved motif (HxxEHx75-80E) that provides selective antiaggregating activity against polyQ-containing proteins while leaving healthy proteins unaffected. The peptide's specific sequence and structural properties enable it to target only pathological aggregates, resolving the contradiction between therapeutic effect and lack of side effects.
Solution Approach 2:
The patent extracts the essential functional motif from the full-length stromal processing peptidase enzyme, isolating only the critical HxxEHx75-80E region responsible for Zn2+ binding and antiaggregating activity. This extracted peptide fragment maintains therapeutic efficacy while eliminating the harmful effects of full enzyme expression, achieving selective action against pathological proteins.
2Object-affected harmful factors
If a drug targets pathological proteins specifically, then side effects are reduced, but the complexity of achieving selective targeting increases
Solution Approach 1:
The patent applies universality by designing a peptide that performs multiple functions through a single conserved motif: Zn2+ binding, antiaggregating activity, and selective targeting of polyQ-containing proteins. This multi-functional design achieves specific targeting without requiring complex delivery systems or multiple components, thereby reducing overall system complexity while maintaining high selectivity.
Solution Approach 2:
The patent utilizes parameter changes by modifying the peptide sequence to preserve the conserved HxxEHx75-80E motif while optimizing other regions for enhanced stability and activity. By carefully adjusting peptide parameters (sequence, length, structural constraints), the invention achieves selective targeting with minimal complexity, avoiding the need for complex formulation or delivery mechanisms.
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 protein effectively reduces the aggregation of pathological proteins, thereby decreasing neurotoxicity and providing a therapeutic option for neurodegenerative diseases like Huntington's without the side effects of affecting healthy protein levels.
Implementation Method 1
The protein comprises a Zn2+-binding region, wherein the conserved motif is HxxEHx75-80E
Data Source
AI summary
The present invention provides an isolated protein exhibiting an antiaggregating activity and/or disaggregating activity toward a target protein comprising an extended polyQ stretch. The protein comprises a Zn2+-binding region, wherein the conserved motif is HxxEHx75-80E and x is any amino acid. The nucleic acid construct encoding said protein as well as the corresponding mRNA sequence are also provided. The protein, the nucleic acid construct or mRNA sequence are for use in a method for prevention or treatment of a neurodegenerative disease that is caused by aggregates comprising at least one target protein and/or by the mRNA encoding for said target protein, wherein the target protein causes e.g. Huntington's disease or Machado-Joseph disease.