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.