Expression of alpha-synuclein in non-apoptotic, slowly degenerating facial motoneurones

J Neurocytol. 2001 Jun;30(6):515-21. doi: 10.1023/a:1015697318437.


The discovery that missense mutations in the alpha-synuclein gene represent a rare genetic cause of Parkinson's disease (PD) has had significant impact on the development of research into neurodegenerative disorders. It is becoming increasingly clear that alpha-synuclein plays a central role in the pathological process, which causes Lewy body formation and neurodegeneration in PD. Importantly, there is evidence to suggest that mutated alpha-synuclein is toxic to both nerve cells and glia. However, the regulation and function of wild-type alpha-synuclein are as yet ill defined. Using the facial nerve axotomy model, we have addressed the question whether the expression of alpha-synuclein in nerve cells may change in response to injury. We were particularly interested in testing the hypothesis that the severity of neuronal injury had an effect on alpha-synuclein metabolism. Facial nerve cut and crush, respectively, were performed in adult rats where normal facial motoneurones do not express alpha-synuclein. Following axotomy, a subset of facial motoneurones newly expressed high levels of alpha-synuclein immunoreactivity in their cell body and, occasionally, their nucleus. Significantly more nerve cells were labelled following facial nerve transection than following facial nerve crush. Confocal microscopy revealed a granular pattern of alpha-synuclein aggregation in degenerating nerve cells. Interestingly, the observed cell death phenotype was clearly non-apoptotic and developed over days or weeks rather than hours. Thus, axotomy of adult rat facial motoneurones triggers de novo expression of alpha-synuclein and this expression is associated with a non-apoptotic, slow form a neurodegeneration. In addition, the extent of alpha-synuclein expression is related to the severity of neuronal injury.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis / physiology
  • Axotomy / methods
  • Facial Nerve / metabolism*
  • Facial Nerve / pathology
  • Motor Neurons / metabolism*
  • Motor Neurons / pathology
  • Nerve Crush / methods
  • Nerve Degeneration / metabolism*
  • Nerve Degeneration / pathology
  • Nerve Tissue Proteins / biosynthesis*
  • Rats
  • Rats, Inbred Lew
  • Synucleins
  • alpha-Synuclein


  • Nerve Tissue Proteins
  • Snca protein, rat
  • Synucleins
  • alpha-Synuclein