How is alpha-synuclein cleared from the cell?

Research output: Contribution to journalReview article


The levels and conformers of alpha-synuclein are critical in the pathogenesis of Parkinson's Disease and related synucleinopathies. Homeostatic mechanisms in protein degradation and secretion have been identified as regulators of alpha-synuclein at different stages of its intracellular trafficking and transcellular propagation. Here we review pathways involved in the removal of various forms of alpha-synuclein from both the intracellular and extracellular environment. Proteasomes and lysosomes are likely to play complementary roles in the removal of intracellular alpha-synuclein species, in a manner that depends on alpha-synuclein post-translational modifications. Extracellular alpha-synuclein is cleared by extracellular proteolytic enzymes, or taken up by neighboring cells, especially microglia and astrocytes, and degraded within lysosomes. Exosomes, on the other hand, represent a vehicle for egress of excess burden of the intracellular protein, potentially contributing to the transfer of alpha-synuclein between cells. Dysfunction in any one of these clearance mechanisms, or a combination thereof, may be involved in the initiation or progression of Parkinson's disease, whereas targeting these pathways may offer an opportunity for therapeutic intervention. (Figure presented.).


  • Leonidas Stefanis
  • Evangelia Emmanouilidou
  • Marina Pantazopoulou
  • Deniz Kirik
  • Kostas Vekrellis
  • George K. Tofaris
External organisations
  • Academy of Athens
  • National and Kapodistrian University of Athens
  • University of Oxford
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Cell and Molecular Biology


  • alpha-synuclein, degradation, exosomes, lysosomes, proteasome, ubiquitin
Original languageEnglish
Pages (from-to)577-590
JournalJournal of Neurochemistry
Issue number5
Early online date2019
Publication statusPublished - 2019
Publication categoryResearch