Untangling the role of protein misfolding in neurodegeneration

Neurodegenerative diseases including Alzheimer’s, Parkinson’s and Huntington;s diseases are characterised the deposition and accumulation of misfolded proteins intra- or extracellularly. How the abnormal protein assembly is triggered and how these assembled structures exert neuronal damage remains unclear. Our work aims to uncover the chemical and structural changes that accompany protein self-assembly in vitro and how these species  interact with, and transmit, between neuronal cells. Protein misfolding leads to the assembly of normally soluble proteins to form amyloid fibrils and these share a highly stable, core beta-sheet structure. However, the toxic entity is thought to be small oligomeric species and the toxic mechanism may be due to the assembly process itself. I will discuss the in vitro and in cell studies that we have conducted to gain an understanding of the role of protein misfolding in neurodegenerative diseases.

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