Original Article

Exp Neurobiol 2009; 18(1): 19-25

Published online June 30, 2009

© The Korean Society for Brain and Neural Sciences

Topographical Propagation of Ձ-synuclein Pathology in Parkinson's Disease: Phenomenology and Hypothetical Mechanism

Minsuk Hyun and Seung-Jae Lee*

Department of Biomedical Science and Technology, IBST, Konkuk University, Seoul 143-701, Korea

Correspondence to: *To whom correspondence should be addressed.
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Parkinson's disease is an age-related, slowly progressing neurodegenerative disorder characterized by abnormal deposition of aggregated Ձ-synuclein in neuronal cell bodies (Lewy bodies) and neurites (Lewy neurites), as well as in glia. Based on semiquantitative assessment of Lewy pathologies in autopsy samples, a staging system was proposed indicating a highly predictable sequence of pathological progression. This staging system implicates a propagation of Ձ-synuclein aggregation throughout the brain with an ascending pattern from lower brain stem to neocortex. The underlying mechanism for the pathological propagation is unknown. However, the recent discoveries on the secretion of neuronal Ձ-synuclein and subsequent uptake of the protein by neighboring cells propose an interneuronal transmission of Ձ-synuclein aggregates as a novel mechanism for the spread of Lewy pathology in PD. Elucidation of this mechanism is likely to identify novel therapeutic strategies that halt the progression of PD.

Keywords: lewy body, protein aggregation, exocytosis, endocytosis