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

S. Bhattacharya, D. Thompson Department of Physics, Bernal Institute, University of Limerick, V94 T9PX, Ireland

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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 neu rodegenerative 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 polymor phic 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 mod elling 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 com mon proteinopathies, including Alzheimer’s and Parkinson’s diseases, which could potentially aid in molecular-level understanding of disease pathologies. Predictive computational modelling of amyloid and tau protein assemblies in Alzheimer’s disease and-synuclein protein assemblies in Parkinson’s disease highlights the potential for identification and characterisation of new therapeutic targets for currently incurable neurodegeneration.

DOI:10.12693/APhysPolA.145.S37 topics: proteinopathies, self-assembly, computational modelling, molecular dynamics simulations