Selective cellular vulnerability and resilience in amyloidosis: insights from the 2025 International Society of Amyloidosis Workshop
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Discussion
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Implication
Expert workshop review reveals how precursor sequences, tissue microenvironments, and proteostatic capacity govern amyloid organ targeting, highlighting novel therapeutic avenues.
Key Points
- To review and define the mechanisms underlying organ-specific targeting, cellular vulnerability, and tissue resilience to amyloid toxicity and deposition.
- Synthesized molecular, structural, and physiological findings from the 2025 International Society of Amyloidosis Workshop.
- Evaluated cryo-electron microscopy structural data, tissue microenvironment interactions, and cellular toxicity models across localized and systemic amyloidosis.
- Amyloid precursor amino acid sequence dictates organ tropism, while cryo-electron microscopy demonstrates shared fibril architectures across different affected tissues.
- Cellular uptake of precursors triggers lysosomal dysfunction, mitochondrial impairment, and oxidative stress, disproportionately injuring cardiomyocytes and mesangial cells.
- Interactions with extracellular components (glycosaminoglycans, collagen) alongside age-related declines in proteostasis capacity collectively drive organ-specific vulnerability.
Cite This Study
Giampaolo Merlini (2026) studied this question.