Heat resistant microorganisms and Parkinson’s disease
17.05.2013
Some marine microorganisms thrive at temperatures near 100ºC. These microorganisms synthesize unique solutes presumably used for protection against heat damage, making them interesting sources of protein stabilizers for many applications. While many tests have been performed in vitro, researchers believed it was important to examine the anti-aggregation properties of these compounds in the overcrowded cytoplasm of living cells. Now, researchers from the Cell Physiology & NMR Lab in collaboration with Cell and Molecular Neuroscience Unit at IMM, Lisbon, have looked into the effects of one of these solutes – mannosylglycerate – in a yeast model of Parkinson´s disease and found that it reduces the formation of α synuclein inclusions, a typical marker of Parkinson’s. The work is published in Biochimica Biophysica Acta – General Subjects (IF= 5.0).
The Cell Physiology & NMR Lab has been studying the strategies of osmo- and thermo-adaptation of hyper/thermophilic Bacteria and Archaea for some time and has shown that they accumulate unique negatively charged solutes not found as part of stress adaptation in moderate environments. It appears as though microorganisms adapted to hot environments evolved to synthesize the most effective protectors against heat damage, i.e., ionic solutes. Among the solutes closely associated with thermophily, mannosylglycerate stands out for its great ability to stabilize a variety of model proteins and, for that reason, this solute was selected to study the effect on the formation of α-synuclein inclusions in a yeast model of Parkinson´s disease. α-Synuclein is the major component of the intraneuronal inclusions found in the brains of patients afflicted with this devastating disorder.
In this work, S. cerevisiae cells, expressing α-Syn tagged with a green fluorescent protein, were further engineered to synthesize mannosylglycerate. Fluorescence microscopy was used to assess the number of cells with fluorescent foci. There was a 3.3-fold decrease in α-Syn inclusion formation and this reduction was accompanied by attenuation of the α-Syn-induced cytotoxicity. It is concluded that mannosylglycerate acts as a chemical chaperone and the stabilization mechanism involves direct solute/protein interactions. This is the first demonstration that this ionic solute, closely associated with stress adaptation in hyper/thermophiles, acts as a potent chemical chaperone in vivo, preventing protein misfolding/aggregation. The usefulness of these findings to the development of new drugs against protein-misfolding disorders remains undetermined.
ORIGINAL ARTICLE
Biochimica Biophysica Acta – General Subjects (2013) 1830, 4065-4072
Inhibition of formation of α-synuclein inclusions by mannosylglycerate in a yeast model of Parkinson's disease
Cristiana Faria, Carla D. Jorge, Nuno Borges, Sandra Tenreiro, Tiago F. Outeiro and Helena Santos
