Recent Advances in Mapping Protein Self-Assembly and Aggregation for Common Proteinopathies

This is the authors' abstract. We don't add key points for this paper.

The accumulation of abnormal conformation by brain peptides and proteins followed by their aberrant self-assembly into insoluble aggregates is the hallmark of "proteinopathies", common across many neurodegenerative disorders. Experiments suggest that soluble low-molecular-weight oligomers formed in the early stages of assembly are neurotoxic, and hence, drug targets. However, the inherent polymorphic nature of these short-lived oligomers restricts their experimental characterisation in pathological protein self-assembly pathways. Here, we shed light on the latest contributions from atomic-level modelling techniques, such as computer-based molecular dynamics simulations in bulk solution and on surfaces, which are guiding experimental efforts to map early stages of protein self-assembly in common proteinopathies, including Alzheimer's and Parkinson's diseases, which could potentially aid in molecular-level understanding of disease pathologies. Predictive computational modelling of amyloid-β and tau protein assemblies in Alzheimer's disease and α-synuclein protein assemblies in Parkinson's disease highlights the potential for identification and characterisation of new therapeutic targets for currently incurable neurodegeneration.