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Updated: Jan 12, 2026

Interview: Protein Folding and Studies of Neurodegenerative Diseases
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Rethinking neurodegeneration through a co-proteinopathy lens.

Yu P Zhang1, Shekhar Kedia1, David Klenerman1

  • 1Yusuf Hamied Department of Chemistry, University of Cambridge, Lensfield Road, Cambridge CB2 1EW, UK; UK Dementia Research Institute at Cambridge, Cambridge CB2 0XY, UK.

Trends in Neurosciences
|November 7, 2025
PubMed
Summary

Neurodegenerative diseases involve complex interactions between multiple misfolded proteins, not just single culprits. A new co-proteinopathy framework offers a more realistic approach to understanding and treating these conditions.

Keywords:
Alzheimer’s diseaseParkinson’s diseaseamyotrophic lateral sclerosiscoaggregationprotein aggregationproteostasis

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Area of Science:

  • Neuroscience
  • Biochemistry
  • Pathology

Background:

  • Neurodegenerative diseases are traditionally viewed as distinct proteinopathies, focusing on single proteins like amyloid-β, tau, α-synuclein, or TDP-43.
  • Decades of therapeutic development based on this single-protein paradigm have yielded modest clinical outcomes.
  • Emerging evidence indicates that protein aggregates frequently coexist and interact, influencing each other's pathogenicity.

Purpose of the Study:

  • To propose a novel co-proteinopathy framework for understanding neurodegeneration.
  • To shift the paradigm from isolated protein disorders to an interactive network of misfolded proteins.
  • To advocate for research methodologies that capture the complexity of protein interactions in neurodegenerative diseases.

Main Methods:

  • Review of existing literature on protein aggregation in neurodegenerative diseases.
  • Conceptual development of the co-proteinopathy framework.
  • Emphasis on the need for multiplexed quantification techniques.
  • Highlighting the importance of advanced disease models.

Main Results:

  • The single-protein paradigm is insufficient to explain the complexity of neurodegeneration.
  • Protein aggregates interact and modulate pathogenicity in a network-like manner.
  • A co-proteinopathy framework provides a more accurate representation of disease mechanisms.

Conclusions:

  • Neurodegeneration should be viewed as a co-proteinopathy, an interactive network of misfolded proteins.
  • This framework necessitates multiplexed protein quantification and more complex disease models.
  • The co-proteinopathy perspective offers a foundation for developing more effective next-generation neurodegenerative treatments.