How do protein aggregates escape quality control in neurodegeneration?

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.

Automated summary

Protein aggregation is a characteristic feature of neurodegenerative diseases. The protein quality control system usually prevents misfolding and accumulation of proteins, but this control mechanism is somehow evaded in diseases. This review discusses the role of protein quality control in protein aggregation and neurodegeneration, with a particular focus on Tau protein in Alzheimer's disease and other tauopathies. Recent advances in amyloid fibril structures and the process of fibril formation through phase separation are also explored, providing new insights into the role of protein quality control in protein aggregation diseases.