How do protein aggregates escape quality control in neurodegeneration?

Margreet B. Koopman, Luca Ferrari, Stefan G.D. Rüdiger*

*Corresponding author for this work

Research output: Contribution to journalReview articlepeer-review


Protein aggregates are hallmarks of neurodegenerative diseases. The protein quality control (PQC) system normally prevents proteins from misfolding and accumulation; however, proteins somehow escape this control on disease. Here we review advances in the role of PQC in protein aggregation and neurodegeneration. We focus primarily on the protein Tau, which aggregates in Alzheimer's disease (AD) and other tauopathies. We also examine recent advances in amyloid fibril structures and the process of fibril formation via phase separation, which are shedding new light on the role of PQC in protein aggregation diseases. While specific components of the quality control system appear to be altered in disease, most chaperones and degradation factors are unchanged at the cellular end stage. Advancing the understanding of quality control factors in neurodegeneration, particularly in the early stages of disease, is among the key challenges for neurodegeneration research.

Original languageEnglish
Pages (from-to)257-271
Number of pages15
JournalTrends in Neurosciences
Issue number4
Publication statusPublished - Apr 2022


  • Alpha-synuclein
  • Cryo-em structures
  • Disaggregation
  • Disease
  • Fibrils
  • Phase-separation
  • Proteasome
  • Secondary nucleation
  • Selective autophagy
  • Tau


Dive into the research topics of 'How do protein aggregates escape quality control in neurodegeneration?'. Together they form a unique fingerprint.

Cite this