Impairment of microtubule-dependent trafficking by overexpression of α-synuclein

He J. Lee, Farnaz Khoshaghideh, Stephen Lee, Seung-Jae Lee

Research output: Contribution to journalArticle

104 Citations (Scopus)

Abstract

Abnormal accumulation of α-synuclein (α-syn) has been linked to several neurological disorders, including Parkinson's disease (PD). However, the underlying mechanism by which α-syn accumulation affects neuronal function and survival remains unknown. Here, we provide data suggesting a possible effect of aggregated α-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 α-syn. This effect of α-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 α-syn and tubulins, from which actin was excluded. These studies suggest that the MT system is a potential target of α-syn, and impairment of this system might have impacts on neuronal structure and function.

Original languageEnglish
Pages (from-to)3153-3162
Number of pages10
JournalEuropean Journal of Neuroscience
Volume24
Issue number11
DOIs
StatePublished - 1 Dec 2006

Fingerprint

Synucleins
Microtubules
Spinal Ganglia
Neurites
Tubulin
Nervous System Diseases
Actin Cytoskeleton
Neurodegenerative Diseases
Parkinson Disease
Actins
Neurons
Survival

Keywords

  • Neurodegeneration
  • Parkinson's disease
  • Protein aggregation
  • SH-SY5Y

Cite this

Lee, He J. ; Khoshaghideh, Farnaz ; Lee, Stephen ; Lee, Seung-Jae. / Impairment of microtubule-dependent trafficking by overexpression of α-synuclein. In: European Journal of Neuroscience. 2006 ; Vol. 24, No. 11. pp. 3153-3162.
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Impairment of microtubule-dependent trafficking by overexpression of α-synuclein. / Lee, He J.; Khoshaghideh, Farnaz; Lee, Stephen; Lee, Seung-Jae.

In: European Journal of Neuroscience, Vol. 24, No. 11, 01.12.2006, p. 3153-3162.

Research output: Contribution to journalArticle

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