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Potential applications of stress solutes from extremophiles in protein folding diseases and healthcare

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Abstract

Protein misfolding, aggregation and deposition in the brain, in the form of amyloid, are implicated in the etiology of several neurodegenerative disorders, such as Alzheimer’s, Parkinson’s and prion diseases. Drugs available on the market reduce the symptoms, but they are not a cure. Therefore, it is urgent to identify promising targets and develop effective drugs. Preservation of protein native conformation and/or inhibition of protein aggregation seem pertinent targets for drug development. Several studies have shown that organic solutes, produced by extremophilic microorganisms in response to osmotic and/or heat stress, prevent denaturation and aggregation of model proteins. Among these stress solutes, mannosylglycerate, mannosylglyceramide, di-myo-inositol phosphate, diglycerol phosphate and ectoine are effective in preventing amyloid formation by Alzheimer’s Aβ peptide and/or α-synuclein in vitro. Moreover, mannosylglycerate is a potent inhibitor of Aβ and α-synuclein aggregation in living cells, and mannosylglyceramide and ectoine inhibit aggregation and reduce prion peptide-induced toxicity in human cells. This review focuses on the efficacy of stress solutes from hyper/thermophiles and ectoines to prevent amyloid formation in vitro and in vivo and their potential application in drug development against protein misfolding diseases. Current and envisaged applications of these extremolytes in neurodegenerative diseases and healthcare will also be addressed.

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Acknowledgments

This work was funded by the Fundação para a Ciência e a Tecnologia (FCT), POCTI, Portugal, PTDC/BBB-BEP/2532/2012, SFRH/BPD/110847/2015, INCENTIVO/EQB/LA0004/2014 and UID/CBQ/04612/2013 (MOSTMICRO). The NMR spectrometers are part of The National NMR Facility, supported by Fundação para a Ciência e a Tecnologia (RECI/BBB-BQB/0230/2012). Cristiana Faria is acknowledged for acquiring fluorescence images.

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  1. Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República-EAN, 2780-157, Oeiras, Portugal

    Carla D. Jorge, Nuno Borges & Helena Santos

  2. Bitop AG, Stockumer Straße 28, 58453, Witten, Germany

    Irina Bagyan & Andreas Bilstein

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  1. Carla D. Jorge
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  2. Nuno Borges
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Correspondence to Carla D. Jorge.

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Jorge, C.D., Borges, N., Bagyan, I. et al. Potential applications of stress solutes from extremophiles in protein folding diseases and healthcare. Extremophiles 20, 251–259 (2016). https://doi.org/10.1007/s00792-016-0828-8

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