Disulfide Bonding in Neurodegenerative Misfolding Diseases

Figure 2

Schematic representation of the role of disulfide bonds (S-S) and disulfide bonding enzymes (PDIs) in the misfolding and aggregation of proteins involved in neurodegenerative misfolding diseases. Disulfide bonds stabilize the monomeric protein slowing down the population of aggregation-prone conformations. They also mediate in many cases the formation of aggregates by intermolecular disulfide bonds. PDIs, instead, are upregulated in the presence of protein aggregation as a general response to cellular stress and UPR activation. In some cases PDIs also interact specifically with the aggregating proteins or the aggregates. (Adapted from [1]).