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α-Synuclein and Lewy pathology in Parkinson's disease.
Curr Opin Neurol. 2015 Aug; 28(4):375-81.CO

Abstract

PURPOSE OF REVIEW

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.

RECENT FINDINGS

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.

SUMMARY

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+Show Affiliations

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.No affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't
Review

Language

eng

PubMed ID

26110807

Citation

Kalia, Lorraine V., and Suneil K. Kalia. "Α-Synuclein and Lewy Pathology in Parkinson's Disease." Current Opinion in Neurology, vol. 28, no. 4, 2015, pp. 375-81.
Kalia LV, Kalia SK. Α-Synuclein and Lewy pathology in Parkinson's disease. Curr Opin Neurol. 2015;28(4):375-81.
Kalia, L. V., & Kalia, S. K. (2015). Α-Synuclein and Lewy pathology in Parkinson's disease. Current Opinion in Neurology, 28(4), 375-81. https://doi.org/10.1097/WCO.0000000000000215
Kalia LV, Kalia SK. Α-Synuclein and Lewy Pathology in Parkinson's Disease. Curr Opin Neurol. 2015;28(4):375-81. PubMed PMID: 26110807.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - α-Synuclein and Lewy pathology in Parkinson's disease. AU - Kalia,Lorraine V, AU - Kalia,Suneil K, PY - 2015/6/26/entrez PY - 2015/6/26/pubmed PY - 2016/4/7/medline SP - 375 EP - 81 JF - Current opinion in neurology JO - Curr Opin Neurol VL - 28 IS - 4 N2 - PURPOSE OF REVIEW: 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. RECENT FINDINGS: 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. SUMMARY: 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. SN - 1473-6551 UR - https://www.unboundmedicine.com/medline/citation/26110807/α_Synuclein_and_Lewy_pathology_in_Parkinson's_disease_ L2 - https://doi.org/10.1097/WCO.0000000000000215 DB - PRIME DP - Unbound Medicine ER -