The interaction of small heat shock molecular chaperone proteins with a-synuclein

Protein homeostasis, or proteostasis, is the process of maintaining the conformational and functional integrity of the proteome. Proteostasis is preserved in the face of stress by a complex network of cellular machinery which acts to maintain proteins in their native state, enabling them to perform their biological function. Failure of the proteostasis network can result in the accumulation of non-native (misfolded) proteins, leading to their aggregation and deposition. For example, the amyloid fibrillar aggregation of the protein α-synuclein (α-syn) into Lewy bodies and Lewy neurites is associated with neurodegenerative diseases, classified as α-synucleinopathies, which include Parkinson\u27s disease and dementia with Lewy bodies. The small heat shock proteins (sHsps) are a family of molecular chaperones that are one of the cell\u27s first lines of defence against protein aggregation. They act to stabilise partiallyfolded protein intermediates, in an ATP-independent manner, to maintain cellular proteostasis under stress conditions. Thus, the sHsps are ideally suited to protect against α-syn aggregation, however, they fail to do so in the context of the α-synucleinopathies. Therefore, this project aimed to characterise the ability of the canonical sHsps, αB-crystallin (αB-c) and Hsp27, to prevent α-syn aggregation, both in vitro and in a neuronal cell model