Post-translational modifications regulate conformational polymorphism of protein aggregates associated with neurodegenerative diseases

<p indent="0mm">The conformational polymorphism of amyloid aggregates is of great significance in the pathogenesis of neurodegenerative diseases and the development of targeted drugs. Conformational polymorphism is the basic structural feature of amyloid aggregates and regulated by multiple factors. Among them, post-translational modification, as a key regulatory factor, endows aggregates with rich conformational diversity by regulating the aggregation dynamics and aggregate structure of amyloid. Here we review the new high-resolution structural analysis methods developed in recent years to analyze the conformational polymorphism of amyloid aggregates, and introduce the new progress in the study of the structural characteristics and regulatory mechanisms of the conformational polymorphism of amyloid aggregates. This review summarizes the heterogeneous effects of amyloid post-translational modifications and their key role in the pathological mechanisms of neurodegenerative diseases, illustrates the important regulatory mechanisms of post-translational modifications on the conformational polymorphism of amyloid aggregates, and analyzes the limitations and challenges of this research field at this stage.