Abstract
α-Synuclein (α-syn) is a major component of inclusion bodies in Parkinson's disease (PD) and other synucleinopathies. To clarify the possible roles of α-syn in the molecular pathogenesis of neurodegenerative diseases, we have established a novel cellular model based on the differentiation of SH-SY5Y cells that overexpress α-syn. In the presence of ferrous iron, differentiation of the cells led to the formation of large perinuclear inclusion bodies, which developed from scattered small aggregates seen in undifferentiated cells. The iron-induced α-syn-positive inclusions co-localized largely with ubiquitin, and some of them were positive for nitrotyrosine, lipid, γ-tubulin and dynein. Notably, treatment with nocodazole, a microtubule depolymerizing agent, interrupted the aggregate formation but led to a concomitant increase of apoptotic cells. Therefore, it appears that an intracellular retrograde transport system via microtubules plays a crucial role in the aggregate formation and also that the aggregates may represent a cytoprotective response against noxious stimuli. This cellular model will enable better understanding of the molecular pathomechanisms of synucleinopathy.
Original language | English |
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Pages (from-to) | 51-59 |
Number of pages | 9 |
Journal | Brain research |
Volume | 1013 |
Issue number | 1 |
DOIs | |
Publication status | Published - 2004 Jul 2 |
Keywords
- Aggregation
- CAT
- Degenerative disease: Parkinson's
- Disorders of the nervous system
- Iron
- LBs
- Lewy bodies
- Lewy body
- Neuroblastoma
- PD
- Parkinson's disease
- WT
- wild-type
- α-Synuclein
- α-syn
- α-synuclein
ASJC Scopus subject areas
- Neuroscience(all)
- Molecular Biology
- Clinical Neurology
- Developmental Biology