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

Minsuk Hyun, Seung-Jae Lee
2009 Experimental Neurobiology  
Parkinson's disease is an age-related, slowly progressing neurodegenerative disorder characterized by abnormal deposition of aggregated α-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 α-synuclein aggregation throughout the
more » ... 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 α-synuclein and subsequent uptake of the protein by neighboring cells propose an interneuronal transmission of α-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.
doi:10.5607/en.2009.18.1.19 fatcat:kuj5wdf2vvcmrees2c7gwhuzsi