CCNY Protein Synaptic Localization via Palmitoylation

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Solution Overview

Problem

Current methods lack effective regulation of CCNY protein localization to synapses and do not adequately address cognitive diseases or enhance memory.

Innovation Solution

Regulating the localization of CCNY protein to synapses through palmitoylation, specifically by modifying cysteine residues at positions 7 and 8 with serine or alanine, using palmitoyl acyltransferases like DHHC2, to alter its postsynaptic localization and function.

Engineering Contradictions & Design Principles

VSEngineering Contradiction Analysis

1Reliability

If CCNY protein is palmitoylated at cysteine residues 7 and 8, then CCNY protein is localized to synapses and functions in neuronal processes, but this localization cannot be regulated to prevent or treat cognitive diseases

Engineering Contradiction:
ImproveCCNY protein localization to synapsesVSAvoidregulation of CCNY protein localization
Core Design Contradiction:
ReliabilityVSAdaptability or versatility

Solution Approach 1:

The patent applies parameter changes by modifying the amino acid sequence of CCNY protein, specifically substituting cysteine residues at positions 7 and/or 8 with serine or alanine. This substitution changes the palmitoylation status of the protein, preventing its localization to synapses. The parameter being changed is the chemical structure of the protein at specific residues, which directly controls its subcellular localization and functional activity in neuronal processes.

Inventive Principle:
Principle #35Parameter changes

2Productivity

If cysteine residues at positions 7 and 8 are substituted with serine or alanine, then CCNY protein function at synapses is inhibited and memory is enhanced, but the protein cannot be properly localized to synapses

Engineering Contradiction:
Improvememory enhancementVSAvoidsynaptic localization
Core Design Contradiction:
ProductivityVSReliability

Solution Approach 1:

The patent converts the harmful effect of excessive or unregulated CCNY protein activity at synapses into a beneficial outcome. By substituting cysteine residues to prevent palmitoylation and synaptic localization, the invention eliminates the harmful overactivity while enhancing memory function. The 'harm' of preventing proper localization is transformed into the 'benefit' of treating cognitive diseases and enhancing memory, as the unregulated synaptic presence of CCNY appears to be detrimental to optimal cognitive function.

Inventive Principle:
Principle #22Blessing in disguise (Convert harm into benefit)

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 effectively inhibits CCNY protein function at synapses, potentially preventing or treating cognitive diseases and enhancing memory by redirecting its localization to other intracellular compartments.

Implementation Method 1

Palmitoylation is a post-translational lipid modification involving the attachment of a 16-carbon palmitate to a cysteine residue of a protein via a thioesther bond

Methodology Applied
Scientific EffectPalmitoylation: Chemical Bonding

Data Source

PatentUS11161888B2Method for regulating targeting of Cyclin Y (CCNY) protein to synapses
Publication Date: 2021.11.02 KOREA INST OF SCI & TECH
  • US11161888B2 patent drawing
  • US11161888B2 patent drawing
  • US11161888B2 patent drawing

AI summary

The present invention relates to a method for regulating localization of CCNY protein to synapses, comprising palmitoylation of CCNY protein. Specifically, the present invention relates to a method for regulating targeting of CCNY protein to synapses by regulating addition of a palmitoyl group to cysteine at position 7 and/or 8 on the CCNY protein. Therefore, the palmitoylation of CCNY, a postsynaptic protein known to be implicated in synaptic plasticity and learning and memory, is a critical process for CCNY to be localized in postsynaptic spines, and thus it can be found that CCNY plays an important role in synaptic functions.