Protein N-Homocysteinylation Induces the Formation of Toxic Amyloid-Like Protofibrils

Effect of N‐homocysteinylation on physicochemical and cytotoxic properties of amyloid β‐peptide

“…According to recent reports, N-homocysteinylation of the globular proteins can convert the protein structure into a partially unfolded intermediate with a higher tendency to form aggregate [46]. Ab is natively unfolded in monomeric state.…”

Design of protein homocystamides with enhanced tumor uptake properties for 19F magnetic resonance imaging

“…47,58 Far-UV CD spectra of the homocysteinylated albumin differ strongly from those obtained from the unmodified albumin, suggesting that homocysteinylation results in a loss of the -helical content accompanied by an increase in the -sheet content (see Figure 6 and Table 2). On the other hand, our results clearly demonstrate that the fluorinated albumin conjugate retained most of the -helix present in the native protein.…”

“…58 The early aggregates are cytotoxic and induce apoptosis in mammalian cell cultures. In addition, in the last few years, several pieces of evidence have indicated that protein unfolding and aggregation are crucial events leading to the formation of amyloid fibrils associated with a wide range of human pathologies.…”

“…47,58 Modification, such as amidation or arylation, of Hcy residues in N-homocysteinylated albumin can affect protein conformation, as well as its ability to aggregate. Therefore, we tested the aggregation properties of the obtained fluorinated Hсy-HSA conjugates using gel retardation assay.…”

Micronutrient Metabolism in Hemodialysis Patients

“…Further, homocysteine increased the affinity of N-methyl-D-asparate (NMDA) glutamate subreceptors, which indirectly caused the calcium influx (Obeid and Herrmann,206). Increasing evidence shows that homocysteine thiolactone induce protein unfolding and aggregation, and can lead to the formation of amyloid fibrils (Paoli et al, 2010). DNA methylation plays an essential role in maintaining cellular function, and reduced DNA methyltransfrerase may contribute to the development of certain cancers (Davis and Uthus, 2004).…”