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Updated: May 26, 2025
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JUMPn: A Streamlined Application for Protein Co-Expression Clustering and Network Analysis in Proteomics
Published on: October 19, 2021
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Systems-Level Interactome Mapping Reveals Actionable Protein Network Dysregulation Across the Alzheimer's Disease
Sadik Bay1, Anna Rodina1, Florence Haut2
1Chemical Biology Program, Memorial Sloan Kettering Cancer Center, New York, NY 10065, USA.
Research Square
|February 24, 2025
Summary
Epichaperomes drive Alzheimer's disease (AD) progression by disrupting protein networks early, even before symptoms appear. Targeting these epichaperomes with PU-AD therapy can restore network function and reverse cognitive decline in AD.
Area of Science:
- Neuroscience
- Molecular Biology
- Systems Biology
Background:
- Alzheimer's disease (AD) progression involves poorly understood molecular mechanisms.
- AD spans a continuum from preclinical stages to severe cognitive impairment.
Purpose of the Study:
- To map protein-protein interaction (PPI) network dysfunction across the AD spectrum.
- To identify key molecular drivers of AD progression.
- To explore epichaperomes as potential therapeutic targets.
Main Methods:
- Analysis of over 100 human brain specimens, mouse models, and human neurons.
- Systems-level mapping of protein-protein interaction (PPI) networks.
- Investigation of epichaperome formation and function in AD.
Main Results:
- Epichaperomes, chaperone-based scaffolds, emerge early in AD and disrupt critical PPI networks.
- Glutamatergic neuron dysfunction is driven by protein sequestration into epichaperomes.
- Pharmacological disruption of epichaperomes with PU-AD restored network integrity and reversed cognitive deficits.
Conclusions:
- Epichaperomes are central drivers of molecular collapse and network dysfunction in Alzheimer's disease.
- Network-centric therapeutic strategies targeting epichaperomes show promise for disease modification in AD.
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