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Eukaryon

Class Year

2008

Keywords

dying midbrain striatal dopaminergic neurons, neurodegenerative disease, Polymerase chain reaction, Fluorescence Microscopy, dimethyl sulfoxide

Abstract

Lewy bodies of a-synuclein protein are prominent characteristics in the Parkinson's disease (PD) pathology. The mechanism of Lewy body formation and consequent cytotoxicity was studied by Brandis et al. (2006) in a newly developed model organism of fission yeast. Though, the level of a-synuclein expression studied was either high or low, the wild-type and A53T familial mutant of a-synuclein followed the nucleation polymerization theory in the process of misfolding and aggregating. At high concentration, a-synuclein formed cytoplasmic aggregates in a concentration and time-dependent manner. However, these aggregates appeared to be independent of cytotoxicity. In this current study, the fission yeast model is used again but to evaluate a-synuclein misfolding, aggregation, and non-toxic properties when expression is moderate. The results indicate moderate a-synuclein expression to obey the nucleation polymerization model. In light of this study, a-synuclein aggregation requires a necessary threshold concentration. Moderately expressed a-synuclein forms soluble aggregates, but at a slightly lower expression. So far, studies in fission yeast cells show that various concentrations of a-synuclein, neither target the plasma membrane nor are toxic. Because a-synuclein misfolding and aggregation is linked to Parkinson's disease, absence of its toxicity in fission yeast is paradoxical. We expect that a-synuclein toxicity may require a membrane binding capacity. In an attempt to induce a-synuclein's localization to the plasma membrane, the content of phospholipids in yeast was increased. Membrane localization and cytotoxicity were still lacking. Needless to say, fission yeast shed provocative insight into a-synuclein's role in PD pathogenesis.

Disclaimer

Eukaryon is published by students at Lake Forest College, who are solely responsible for its content. The views expressed in Eukaryon do not necessarily reflect those of the College. Articles published within Eukaryon should not be cited in bibliographies. Material contained herein should be treated as personal communication and should be cited as such only with the consent of the author.