Eur J Neurosci. 2006 Dec;24(11):3153-62.

Impairment of microtubule-dependent trafficking by overexpression of
alpha-synuclein.
Lee HJ, Khoshaghideh F, Lee S, Lee SJ.
The Parkinson's Institute, Sunnyvale, CA 94089, USA.

Abnormal accumulation of alpha-synuclein (alpha-syn) has been linked
to several neurological disorders, including Parkinson's disease (PD).
However, the underlying mechanism by which alpha-syn accumulation
affects neuronal function and survival remains unknown. Here, we
provide data suggesting a possible effect of aggregated alpha-syn on
the microtubule (MT) network. Consistent with the MT dysfunction, we
also observed other degenerative changes, such as neuritic
degeneration, trafficking defects, and Golgi fragmentation, which are
common pathological features shared by many human neurodegenerative
diseases. Neuritic degeneration and Golgi fragmentation were confirmed
in primary cultures of dorsal root ganglia (DRG) neurons
overexpressing alpha-syn. This effect of alpha-syn seems to have some
selectivity to the MT system, as actin microfilaments and MT-
independent trafficking remain unaffected. Within the degenerating
neurites, we found numerous spherical co-aggregates of alpha-syn and
tubulins, from which actin was excluded. These studies suggest that
the MT system is a potential target of alpha-syn, and impairment of
this system might have impacts on neuronal structure and function.


PMID: 17156376 [PubMed - indexed for MEDLINE]