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The Parkinson's Disease Protein α‐synuclein Alters the Microenvironment of the Endoplasmic Reticulum in Saccharomyces cerevisiae
Author(s) -
Haak Victoria Melina,
McBride Trevor John,
Haverly Meredith Julia,
Austriaco Nicanor
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.794.5
Subject(s) - saccharomyces cerevisiae , unfolded protein response , endoplasmic reticulum , tunicamycin , protein aggregation , yeast , microbiology and biotechnology , proteostasis , budding yeast , protein folding , biology , chemistry , biochemistry
The protein α‐synuclein forms aggregates in human dopaminergic neurons triggering apoptosis and Parkinson's Disease (PD). To better understand the link between protein aggregate formation and cell death, we have over expressed wild type and two mutant forms, A30P and A53T, of human α‐synuclein in the budding yeast, Saccharomyces cerevisiae . Our experiments suggest that these aggregates trigger the unfolded protein response (UPR) in yeast and that different clinically relevant variants of α‐synuclein up‐regulate the UPR to different degrees. Moreover, we show that the overexpression of α‐synuclein alters the redox state and the calcium dynamics of the yeast ER. Finally, our preliminary data suggests that sub‐lethal doses of tunicamycin and β‐mercaptoethanol, drugs that trigger the UPR, may alleviate the aggregation of α‐synuclein. Our results point to possible pharmacological interventions that may lower protein aggregation in PD. [Our laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.] Support or Funding Information [Our laboratory is supported by grant NIGMS R15 GM110578, awarded to N. Austriaco.] This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .