Treating C. elegans muscle polyQ models with hydroxylamine, icariin and celecoxib derivatives (NG-094, icariside II and OSU-03012, respectively) ameliorated polyQ-mediated protein aggregation and protected against polyQ proteotoxicity [48 50] (Table 1; Figs. 1, 2).
The structural basis of polyQ-mediated protein aggregation is believed to be the formation of "polar zippers", in which β-sheets are stabilised by hydrogen bonds between polar amino acids [25].
Trehalose was initially found active in a screening designed to find inhibitors of polyQ-mediated protein aggregation and was tested with various disaccharides because of the lack of toxicity and the possibility of safe, oral administration (43).
In addition, rab-1 was discovered in genetic screens as a regulator of α-synuclein-mediated protein aggregation in a yeast model and is also effective in neuroprotection in worms and flies [ 58, 59].
The uncoupling mediated by T7 RNAP may in turn mediate protein aggregation.
Among the many factors that have been involved in the mechanisms of MN degeneration are glutamate receptor-mediated excitotoxicity, oxidative stress, mitochondrial dysfunction, neuroinflammation, immune-mediated processes, protein aggregation and axonal transport alterations [ 1, 2], but there is still no satisfactory explanation of why such factors damage predominantly MNs.
The progressive nature of polyQ-mediated toxicity, protein aggregation and general severity of phenotype demonstrated in these models is age- and polyQ-tract-length-dependent, recapitulating critical aspects of polyglutamine expansion diseases in patients.
Revealing the trehalose mediated inhibition of protein aggregation through lysozyme-silver nanoparticle interaction.
Revealing the trehalose mediated inhibition of protein aggregation through lysozyme-silver nanoparticle interaction.. Soft matter.
We then systematically assess the role of the histidine residues in Aβ and how they mediate distinct metal-mediated, oxidative and protein aggregation stresses.
It has identified previously neglected factors as important determinants of the GAG-mediated acceleration of protein aggregation, such as solute molarity and protein∶GAG molar ratio.
