title: α-Synuclein and Lewy pathology in Parkinson's disease.
abstract: OBJECTIVE
  The role of protein aggregates, such as Lewy body inclusions, in the molecular pathogenesis of Parkinson's disease has remained controversial and elusive. The protein α-synuclein is a major component of these inclusions but it can exist in many alternate conformations. Here we review advances in our understanding of the roles of Lewy pathology and α-synuclein in Parkinson's disease.
  
  
  RESULTS
  Recent work has demonstrated that certain α-synuclein conformations are directly toxic to neurons and may also propagate Lewy pathology within the nervous system. Investigation into clinicopathological correlates in rare genetic forms of Parkinson's disease has revealed that Lewy pathology is associated with nonmotor features but may not contribute to motor symptoms in Parkinson's disease.
  
  
  CONCLUSIONS
  These recent findings open up new avenues of investigation into the molecular pathogenesis of Parkinson's disease. Future work will need to identify the most toxic conformations of α-synuclein and define their relationship to Lewy pathology. This work will be necessary to be able to develop novel therapeutic strategies that target specific pathogenic forms of α-synuclein for disease modification in Parkinson's disease.
authors.affiliation: aDivision of Neurology, Department of Medicine bDivision of Neurosurgery, Department of Surgery cTanz Centre for Research in Neurodegenerative Diseases, University of Toronto dMorton and Gloria Shulman Movement Disorders Clinic and the Edmond J. Safra Program in Parkinson's Disease, Division of Neurology, Department of Medicine eToronto Western Research Institute, Toronto Western Hospital, University Health Network, Toronto, ON, Canada.
authors.forename: Lorraine V
authors.initials: LV
authors.lastname: Kalia
authors.forename: Suneil K
authors.initials: SK
authors.lastname: Kalia
mesh_terms: D001921:Brain / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D016631:Lewy Bodies / Q000473:pathology*; D009474:Neurons / Q000378:metabolism* / Q000473:pathology; D010300:Parkinson Disease / Q000378:metabolism* / Q000473:pathology; D051844:alpha-Synuclein / Q000378:metabolism*
chemical_list: D051844:alpha-Synuclein