oa Modulation of α-synuclein aggregation by the 70 kDa heat shock protein and its various domains

Molecular chaperones assist in maintenance of functional proteome in vivo and represent the first line of defense against protein misfolding and aggregation in the case of protein misfolding disease. The influence of the stress-induced protein Hsp70 on alpha synuclein aggregation, the primary component of Lewy body's involvement in Parkinson's disease, has been notably investigated. We present in this paper, the in vitro characterization of the effect of the constitutively expressed chaperone Hsc70 and its various domains on alpha synuclein aggregation using ThT assay, AFM, DLS and Cell viability assays. The results show that Hsc70 and C-terminal domains studied are able to inhibit the aggregation of alpha synuclein albeit at different rates and this indicating that efficiency the N-terminal ATPase domain is indispensable. We demonstrate the importance of the Hsc70 C-terminal lid for the full action of Hsc70. This lid might be necessary to bind to α-syn monomer and/or small aggregates and then retard the fibril elongation. We show also a reduced cellular toxicity of alpha synuclein in presence of Hsc70 and its domains with different rates.