The paradoxical cell biology of alpha-Synucle

Results Probl Cell Differ. 2009:48:159-72. doi: 10.1007/400_2009_23.


Synucleinopathies are a group of neurodegenerative diseases characterized by accumulation and aggregation of the protein alpha-synuclein in neuronal perikarya and processes. In contrast to the proximal localization of alpha-synuclein in diseased states, under physiologic conditions, the bulk of alpha-synuclein is present in distant presynaptic terminals. Thus, pathologic conditions lead to mislocalization and aggregation of alpha-synuclein in neuronal cell bodies, and an outstanding question relates to the cell-biological mechanisms that can lead to such mislocalization. Like most other synaptic proteins, alpha-synuclein is synthesized in the neuronal perikarya and then transported into axons and synaptic domains. Accordingly, it has been hypothesized that disturbances in biogenesis/axonal transport or presynaptic targeting of alpha-synuclein can lead to its mislocalization in diseased states. In this chapter, key observations that lead to this hypothesis are presented in addition to a review of some recent literature that has directly addressed this issue. Finally, conflicting results that have resulted from such studies are also highlighted, and a view is offered to reconcile these controversies.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Animals
  • Dementia / physiopathology
  • Humans
  • Neurodegenerative Diseases / physiopathology*
  • alpha-Synuclein / physiology*


  • alpha-Synuclein