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