alpha-synuclein overexpression and microtubule network dysfunction
 

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]

alpha-synuclein
 

olsen -

when Bill Langston (director of the group that authored this study) spoke at the PAN forum in February, he stated that he thought alpha-synuclein was the key to PD - but the mechanism was far from clear. it was really funny - someone in the crowd asked him something like, "what is the role of alpha-synuclein?" and he answered, "if I knew that, then I would be in Stockholm right now!" sounds like their research is coming closer; maybe that Nobel will be his one day. we can only hope.

thanks for posting this.