HAT Activators for Neurodegenerative Disorders
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Solution Overview
Problem
Current treatments for cognitive neurodegenerative disorders, such as Alzheimer's disease, are inadequate in addressing synaptic dysfunction and amyloid-beta peptide accumulation due to limitations in histone acetyltransferase (HAT) activators that are not selectively active and permeable across the blood-brain barrier.
Innovation Solution
Development of compounds with high selectivity and blood-brain-barrier permeability, specifically histone acetyltransferase (HAT) activators of Formula (I), (II), (III), and (IV), which modulate histone acetylation to treat conditions associated with amyloid-beta peptide deposits, including Alzheimer's disease, by administering effective amounts to penetrate the blood-brain barrier and increase histone acetylation.
Engineering Contradictions & Design Principles
Engineering Contradiction Analysis
1Reliability
If HAT activators are administered to treat cognitive neurodegenerative disorders, then histone acetylation increases and gene activation improves, but the compounds fail to penetrate the blood-brain barrier effectively
Solution Approach 1:
The patent modifies the chemical structure of HAT activator compounds by introducing specific functional groups and molecular weight adjustments to enhance blood-brain barrier permeability while maintaining histone acetyltransferase activation capability. This parameter optimization allows the compounds to cross the BBB and reach their target sites in the brain for effective treatment of cognitive neurodegenerative disorders.
2Reliability
If HAT activators are used to increase histone acetylation, then gene activation and DNA repair improve, but selectivity is reduced leading to off-target effects
Solution Approach 1:
The patent designs HAT activator compounds with specific molecular characteristics and functional group arrangements that enable selective binding to target histone acetyltransferases. This local optimization of compound structure ensures preferential activation of specific HAT enzymes while minimizing off-target effects, thereby improving therapeutic selectivity and reducing unwanted side effects.
3Ease of operation
If current HAT activator treatments are administered, then some cognitive symptoms may improve, but synaptic dysfunction and amyloid-beta accumulation are not adequately addressed
Solution Approach 1:
The patent develops HAT activator compounds with enhanced multi-functional properties that simultaneously address multiple pathological features of cognitive neurodegenerative disorders. These compounds not only activate histone acetylation for gene regulation but also demonstrate ability to mitigate synaptic dysfunction and reduce amyloid-beta peptide accumulation, providing comprehensive therapeutic coverage for complex neurodegenerative conditions.
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 compounds effectively reduce amyloid beta protein deposits and improve memory retention and synaptic plasticity by increasing histone acetylation, thereby treating neurodegenerative diseases and potentially cancer, with minimal side effects due to improved pharmacokinetics and membrane permeability.
Implementation Method 1
Histone Acetyltransferases (HATs) are involved in histone acetylation (leading to gene activation), chromosome decondensation, DNA repair and non-histone substrate modification.
Data Source
AI summary
The invention provides for a method for screening compounds that bind to and modulate a histone acetyltransferase protein. The invention further provides methods for treating neurodegenerative disorders, conditions associated with accumulated amyloid-beta peptide deposits, Tau protein levels, and/or accumulations of alpha-synuclein as well as cancer by administering a HAT-activating compound to a subject.