Protein misassembly leadstothe formation of dysfunctional and toxic molecular species relatingtoneurodegeneration in Parkinson's disease and Alzheimer's disease. Here, we tailoredananochaperone(alpha S-nChap) foralpha-synucleintoregulateitsassembly. The alpha S-nChap is capable of i) specifically recognizingalpha-synuclein; ii) dynamically capturing and stabilizing monomericalpha-synucleinand retarding oligomerization; iii) tightly capturing oligomericalpha-synucleintoprevent fibrillization; and iv) transportingalpha-synucleinoligomerstothe lysosomal degradation system. The regulation ofalpha-synucleinassemblyby alpha S-nChap was studied in vitro. Moreover, the role of alpha S-nChap preventingalpha-synucleinpathology in cells and protecting neurons from apoptosis was investigated. The strategy oftailoringananochaperonetoregulateaberrantassemblyof pathogenic proteins provides important insights into protein misfolding diseases. We foresee that alpha S-nChap has therapeutic value for Parkinson's disease.