Extracellular α-synuclein-a novel and crucial factor in Lewy body diseases

Nat Rev Neurol. 2014 Jan 28. doi: 10.1038/nrneurol.2013.275. [Epub ahead of print]

Lee HJ, Bae EJ, Lee SJ.

Author information

1 Department of Anatomy, School of Medicine, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Korea.

2 Department of Biomedical Science and Technology, Konkuk University, 120 Neungdong-ro, Gwangjin-gu, Seoul 143-701, Korea.

Abstract

Misfolding and intracellular aggregation of α-synuclein are thought to be crucial factors in the pathogenesis of Lewy body diseases (LBDs), such as Parkinson disease. However, the pathogenic modifications of this protein and the mechanisms underlying its activity have not been fully characterized. Recent studies suggest that small amounts of α-synuclein are released from neuronal cells by unconventional exocytosis, and that this extracellular α-synuclein contributes to the major pathological features of LBD, such as neurodegeneration, progressive spreading of α-synuclein pathology, and neuroinflammation. In this article, we review a rapidly growing body of literature on possible mechanisms by which extracellular α-synuclein contributes to LBD pathology, and discuss therapeutic approaches to target this form of α-synuclein to halt disease progression.