title: Potential applications of stress solutes from extremophiles in protein folding diseases and healthcare.
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.
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República-EAN, 2780-157, Oeiras, Portugal. cjorge@itqb.unl.pt.
authors.forename: Carla D
authors.initials: CD
authors.lastname: Jorge
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República-EAN, 2780-157, Oeiras, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Borges
authors.affiliation: Bitop AG, Stockumer Straße 28, 58453, Witten, Germany.
authors.forename: Irina
authors.initials: I
authors.lastname: Bagyan
authors.affiliation: Bitop AG, Stockumer Straße 28, 58453, Witten, Germany.
authors.forename: Andreas
authors.initials: A
authors.lastname: Bilstein
authors.affiliation: Instituto de Tecnologia Química e Biológica António Xavier, Universidade Nova de Lisboa, Av. da República-EAN, 2780-157, Oeiras, Portugal.
authors.forename: Helena
authors.initials: H
authors.lastname: Santos
mesh_terms: D000599:Amino Acids, Diamino / Q000494:pharmacology*; D000682:Amyloid / Q000187:drug effects*; D000818:Animals; D001105:Archaea / Q000378:metabolism*; D001419:Bacteria / Q000378:metabolism*; D005988:Glyceric Acids / Q000494:pharmacology*; D005994:Glycerophosphates / Q000494:pharmacology*; D006801:Humans; D008358:Mannose / Q000031:analogs & derivatives* / Q000494:pharmacology; D057165:Proteostasis Deficiencies / Q000517:prevention & control*; D013312:Stress, Physiological
chemical_list: D000599:Amino Acids, Diamino; D000682:Amyloid; D005988:Glyceric Acids; D005994:Glycerophosphates; C409185:diglycerol phosphate; C402688:mannosylglycerate; C045628:ectoine; D008358:Mannose
keywords: Compatible solutes; Ectoine; Extremolytes; Mannosylglycerate; Neurodegenerative diseases; Protein aggregation