Tailoring a Nanochaperone to Regulate α‐Synuclein Assembly

Abstract Protein misassembly leads to the formation of dysfunctional and toxic molecular species relating to neurodegeneration in Parkinson's disease and Alzheimer's disease. Here, we tailored a nanochaperone (αS‐nChap) for α‐synuclein to regulate its assembly. The αS‐nChap is capable of i) specifically recognizing α‐synuclein; ii) dynamically capturing and stabilizing monomeric α‐synuclein and retarding oligomerization; iii) tightly capturing oligomeric α‐synuclein to prevent fibrillization; and iv) transporting α‐synuclein oligomers to the lysosomal degradation system. The regulation of α‐synuclein assembly by αS‐nChap was studied in vitro. Moreover, the role of αS‐nChap preventing α‐synuclein pathology in cells and protecting neurons from apoptosis was investigated. The strategy of tailoring a nanochaperone to regulate aberrant assembly of pathogenic proteins provides important insights into protein misfolding diseases. We foresee that αS‐nChap has therapeutic value for Parkinson's disease.