Alpha Synuclein Aggregation in a Neurotoxic Model of Parkinson's Disease
Abstract
The cause of Parkinson's disease (PD) is not known but the pattern of neurodegeneration can be replicated by the systemic administration of the neurotoxin 1-methyl-4-phenyl-tetrahydropyridine (MPTP). MPTP inhibits mitochondrial oxidative phosphorylation and causes oxidative injury leading to cell death. Neurons that degenerate in PD develop inclusions called Lewy bodies that are composed of aggregates of a synaptic protein, alpha synuclein. The purpose of this study is to determine how MPTP affects cytoskeletal and synaptic proteins and to study the relationship between oxidative damage and the formation of synuclein aggregates within neurons. We have shown that primates and mice develop alpha synuclein and ubiquitin immunoreactive aggregates in degenerating neurons 7-10 days after MPTP administration. Degenerating neurons are identified using dopamine transporter, and calbindin immunocytochemistry and glial reaction is identified with glial acidic fibrillary protein. Synaptophysin and neurofilament immunoreactivity are not strikingly altered. The neurodegenerative process is associated with increased levels of oxidative markers for DNA, protein and lipids as indicated by immunocytochemistry for 8-hydroxydeoxyguanosine, 3-nitrotyrosine and malondialdehyde respectively. Over the next year we plan to complete time course studies and complete studies to define the cytoskeletal, synaptic and oxidative changes associated with synuclein aggregation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Aug 01, 2001
- Accession Number
- ADA397690
Entities
People
- Neil W. Kowall
Organizations
- Boston University