Format

Send to

Choose Destination
See comment in PubMed Commons below
PLoS One. 2012;7(6):e38545. doi: 10.1371/journal.pone.0038545. Epub 2012 Jun 12.

The role of alpha-synuclein oligomerization and aggregation in cellular and animal models of Parkinson's disease.

Author information

1
Division of Life Science, State Key Laboratory of Molecular Neuroscience, The Hong Kong University of Science and Technology, Hong Kong, China.

Abstract

α-Synuclein (α-syn) is a synaptic protein in which four mutations (A53T, A30P, E46K and gene triplication) have been found to cause an autosomal dominant form of Parkinson's disease (PD). It is also the major component of intraneuronal protein aggregates, designated as Lewy bodies (LBs), a prominent pathological hallmark of PD. How α-syn contributes to LB formation and PD is still not well-understood. It has been proposed that aggregation of α-syn contributes to the formation of LBs, which then leads to neurodegeneration in PD. However, studies have also suggested that aggregates formation is a protective mechanism against more toxic α-syn oligomers. In this study, we have generated α-syn mutants that have increased propensity to form aggregates by attaching a CL1 peptide to the C-terminal of α-syn. Data from our cellular study suggest an inverse correlation between cell viability and the amount of α-syn aggregates formed in the cells. In addition, our animal model of PD indicates that attachment of CL1 to α-syn enhanced its toxicity to dopaminergic neurons in an age-dependent manner and induced the formation of Lewy body-like α-syn aggregates in the substantia nigra. These results provide new insights into how α-syn-induced toxicity is related to its aggregation.

PMID:
22701661
PMCID:
PMC3373518
DOI:
10.1371/journal.pone.0038545
[Indexed for MEDLINE]
Free PMC Article
PubMed Commons home

PubMed Commons

0 comments

    Supplemental Content

    Full text links

    Icon for Public Library of Science Icon for PubMed Central
    Loading ...
    Support Center