Co-proteinopathy in neurodegeneration

In neurodegenerative disease, multiple pathogenic protein aggregates frequently coexist, colocalise, and form heterotypic assemblies that modulate one another’s toxicity. 

Models focused on single protein aggregates do not capture the clinical heterogeneity of neurodegeneration, and therapies targeting a single species have yielded only modest benefits.

A co-proteinopathy framework views neurodegeneration as an interactive network of misfolded proteins rather than as isolated proteinopathies.

Advancing this framework requires multiplexed, quantitative assays in tissues and biofluids alongside model systems calibrated to the in vivo abundance, stoichiometry, and composition of protein aggregates.

Such an approach enables standardised aggregate profiling for disease characterisation and supports multitarget interventions aimed at shared aggregation interfaces and proteostatic pathways.

https://www.cell.com/trends/neurosciences/fulltext/S0166-2236(25)00219-X

https://sciencemission.com/neurodegeneration-and-co-proteinopathy