Journal
FEBS JOURNAL
Volume 289, Issue 8, Pages 2047-2066Publisher
WILEY
DOI: 10.1111/febs.16031
Keywords
Alzheimer's disease; complex diseases; edgetic perturbations in disease; epichaperome; epichaperomics; interactome network dysfunctions; precision medicine; protein connectivity dysfunctions; protein-protein interactions; tissue-specific interactome
Categories
Funding
- NIH [U01 AG032969, R56 AG061869, R56 AG072599, R01 AG067598, P01 AG014449, P01 AG017617, R01 AG043375, P30 CA008748, R01 NS088627, R01 NS112144]
- Coins for Alzheimer's Research
- Commonwealth Foundation for Cancer Research
- Experimental Therapeutics Center of the Memorial Sloan Kettering Cancer Center
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The article discusses the relationship between stressor-induced protein interactome network perturbations and the formation of pathologic scaffolds, proposing how epichaperomics can reliably obtain context-dependent interactomes to advance the definition, understanding, and control of complex disease interactome networks.
The increasingly appreciated prevalence of complicated stressor-to-phenotype associations in human disease requires a greater understanding of how specific stressors affect systems or interactome properties. Many currently untreatable diseases arise due to variations in, and through a combination of, multiple stressors of genetic, epigenetic, and environmental nature. Unfortunately, how such stressors lead to a specific disease phenotype or inflict a vulnerability to some cells and tissues but not others remains largely unknown and unsatisfactorily addressed. Analysis of cell- and tissue-specific interactome networks may shed light on organization of biological systems and subsequently to disease vulnerabilities. However, deriving human interactomes across different cell and disease contexts remains a challenge. To this end, this opinion article links stressor-induced protein interactome network perturbations to the formation of pathologic scaffolds termed epichaperomes, revealing a viable and reproducible experimental solution to obtaining rigorous context-dependent interactomes. This article presents our views on how a specialized 'omics platform called epichaperomics may complement and enhance the currently available conventional approaches and aid the scientific community in defining, understanding, and ultimately controlling interactome networks of complex diseases such as Alzheimer's disease. Ultimately, this approach may aid the transition from a limited single-alteration perspective in disease to a comprehensive network-based mindset, which we posit will result in precision medicine paradigms for disease diagnosis and treatment.
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