HMGB Protein Binding to Abnormal Polyglutamine Aggregates
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Solution Overview
Problem
Current treatments for polyglutamine diseases, such as Huntington's disease, are limited, with few effective substances available, and existing apoptosis inhibitors face clinical challenges due to difficulties in inhibiting protein aggregation within neurons, which is a common feature across various neurodegenerative diseases.
Innovation Solution
The use of HMGB family proteins or their derivatives, which bind to abnormal polyglutamine proteins, preventing their incorporation into nuclear inclusion bodies and maintaining functional protein levels, thereby offering a prophylactic or therapeutic approach by replenishing or inhibiting the binding of HMGB family proteins to these abnormal proteins.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If apoptosis inhibitors are used to treat polyglutamine diseases, then cell death is reduced, but protein aggregation within neurons is not effectively inhibited
Solution Approach 1:
The patent introduces HMGB family proteins as intermediary substances that mediate between abnormal polyglutamine proteins and nuclear inclusion bodies. These proteins bind to abnormal polyglutamine proteins and prevent their incorporation into inclusion bodies, thereby blocking the harmful aggregation process without directly inducing apoptosis inhibition
Solution Approach 2:
The patent extracts the harmful function of abnormal polyglutamine proteins from the nucleus by having HMGB family proteins bind to them and prevent their incorporation into inclusion bodies. This removes the aggregating propensity from the nuclear environment, effectively separating the harmful aggregation function from the normal nuclear processes
2Object-generated harmful factors
If HMGB family proteins bind to abnormal polyglutamine proteins, then functional HMGB protein levels decrease, but protein aggregation is prevented
Solution Approach 1:
The patent applies preliminary action by having HMGB family proteins bind to abnormal polyglutamine proteins before they can be incorporated into nuclear inclusion bodies. This preemptive binding prevents the harmful aggregation process from occurring, while the subsequent depletion of functional HMGB proteins is a consequence rather than a cause of the therapeutic effect
Solution Approach 2:
The patent converts the harmful binding of HMGB family proteins to abnormal polyglutamine proteins (which depletes functional HMGB proteins) into a beneficial outcome. By binding to abnormal proteins, HMGB family proteins prevent their incorporation into inclusion bodies, and this same binding action can be harnessed therapeutically to prevent aggregation without requiring maintenance of high functional HMGB levels
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
This approach potentially prevents or treats polyglutamine diseases by maintaining the functional levels of HMGB family proteins in the nucleus, thereby reducing neurodegeneration and cell death associated with these diseases.
Implementation Method 1
HMGB family proteins bind to abnormal polyglutamine proteins produced in patients with a polyglutamine disease or other neurodegenerative diseases and become incorporated into the nuclear inclusion bodies
Data Source
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AI summary
To provide a prophylactic/therapeutic agent for neurodegenerative diseases (such as polyglutamine diseases), the agent containing an HMGB family protein or a derivative thereof, such as a protein according any one of (a) and (b) below: (a) a protein having the amino acid sequence of SEQ ID NO: 2, 4, 6 or 8; and (b) a protein having an amino acid sequence resulting from deletion, substitution, addition or insertion of one or more amino acids in the amino acid sequence of SEQ ID NO: 2, 4, 6 or 8 and having binding activity to an abnormal polyglutamine protein produced in a neurodegenerative disease.