The molecular chaperones DNAJB6 and Hsp70 cooperate to suppress α-synuclein aggregation

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A major hallmark of Parkinson's disease (PD) is the presence of Lewy bodies (LBs) in certain neuronal tissues. LBs are protein-rich inclusions, in which α-synuclein (α-syn) is the most abundant protein. Since these inclusions are not present in healthy individuals, despite the high concentration of α-syn in neurons, it is important to investigate whether natural control mechanisms are present to efficiently suppress α-syn aggregation. Here, we demonstrate that a CRISPR/Cas9-mediated knockout (KO) of a DnaJ protein, DNAJB6, in HEK293T cells expressing α-syn, causes a massive increase in α-syn aggregation. Upon DNAJB6 re-introduction into these DNAJB6-KO HEK293T-α-syn cells, aggregation is reduced to the level of the parental cells. We then show that the suppression of α-syn aggregation is dependent on the J-domain of DNAJB6, as the catalytically inactive protein, which carries the H31Q mutation, does not suppress aggregation, when re-introduced into DNAJB6-KO cells. We further demonstrate, that the suppression of α-syn aggregation is dependent on the molecular chaperone Hsp70, which is consistent with the well-known function of J-domains of transferring unfolded and misfolded proteins to Hsp70. These data identify a natural control strategy to suppress α-syn aggregation and suggest potential therapeutic approaches to prevent or treat PD and related disorders.


  • Francesco A Aprile
  • Emma Källstig
  • Galina Limorenko
  • Michele Vendruscolo
  • David Ron
  • Christian Hansen
External organisations
  • University of Cambridge
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Neurosciences
Original languageEnglish
Article number9039
JournalScientific Reports
Issue number1
Publication statusPublished - 2017 Dec 1
Publication categoryResearch