Synergistic approaches unraveling regulation and aggregation of intrinsically disordered β-amyloids implicated in Alzheimer’s disease

Ameliorating amyloid aggregation through osmolytes as a probable therapeutic molecule against Alzheimer's disease and type 2 diabetes

“…7 shows the peptide dehydration proles of Ab and hIAPP in the presence of G-HCL and L-PRO, representing the enhanced dehydration in the case of G-HCL, but reduced dehydration in the case of L-PRO. Similar dehydration patterns for Ab in the presence of urea and TMAO were obtained in our previous study, 37 and for a-synuclein, showing the depletion of water from its surface. 81 The distribution of G-HCL and L-PRO around the peptide surface…”

“…One study investigated the role of osmolytes in protein misfolding and the aggregation of amyloid peptides. 37 The effects of urea and TMAO during conformational sampling through REMD helped gain understanding regarding the shis in populations between compact and extended structures. Another study analyzed the effects of osmolytes, using circular dichroism spectroscopic data from Ab fragments, IAPP amyloidogenic fragments, and polyglutamine peptide fragments for conformational analysis and aggregation.…”

“…95 Atomistic simulations showed oligomerization as a result of anti-parallel b-sheet formation between C-terminal segments. The central [20][21][22][23][24][25][26][27][28][29] and Cterminal [30][31][32][33][34][35][36][37] segments aid in maintaining stable secondary structures and encouraging intermolecular interactions. The hydrophobic amino acids (I26 and L27) facilitate oligomeric conformations and help in the elongation of brils.…”

“…The osmolytes G-HCL and L-PRO were used according to models developed by Nozaki and Tanford 78 and at specic concentrations (i.e., 5 M for G-HCL and 2 M for L-PRO), as previously described. 37…”

“…Can common traits be found among osmolytes with stabilizing or destabilizing effects on proteins? To address these questions, and to put the results obtained for urea in our previous work 37 into a more general framework, we investigated the interactions of Ab and hIAPP with another denaturant, guanidine hydrochloride (G-HCL), and a counter-denaturant, L-proline (L-PRO).…”