Mechanisms of Amyloid Proteins Aggregation and Their Inhibition by Antibodies, Small Molecule Inhibitors, Nano-particles and Nano-bodies
Alzheimer's Disease, Amyloidosis, Blood Brain Barrier, Mechanisms of Protein Aggregation, Protein Aggregation
Digital Object Identifier (DOI)
Protein misfolding and aggregation can be induced by a wide variety of factors, such as dominant disease-associated mutations, changes in the environmental conditions (pH, temperature, ionic strength, protein concentration, exposure to transition metal ions, exposure to toxins, posttranslational modifications including glycation, phosphorylation, and sulfation). Misfolded intermediates interact with similar intermediates and progressively form dimers, oligomers, protofibrils, and fibrils. In amyloidoses, fibrillar aggregates are deposited in the tissues either as intracellular inclusion or extracellular plaques (amyloid). When such proteinaceous deposit occurs in the neuronal cells, it initiates degeneration of neurons and consequently resulting in the manifestation of various neurodegenerative diseases. Several different types of molecules have been designed and tested both in vitro and in vivo to evaluate their anti-amyloidogenic efficacies. For instance, the native structure of a protein associated with amyloidosis could be stabilized by ligands, antibodies could be used to remove plaques, oligomer-specific antibody A11 could be used to remove oligomers, or prefibrillar aggregates could be removed by affibodies. Keeping the above views in mind, in this review we have discussed protein misfolding and aggregation, mechanisms of protein aggregation, factors responsible for aggregations, and strategies for aggregation inhibition.
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Citation / Publisher Attribution
International Journal of Biological Macromolecules, v. 186, issue 1, p. 580-590
Scholar Commons Citation
Salahuddin, Parveen; Khan, Rizwan Hasan; Furkan, Mohammad; Uversky, Vladimir N.; Islam, Zeyaul; and Fatima, Munazza Tamkeen, "Mechanisms of Amyloid Proteins Aggregation and Their Inhibition by Antibodies, Small Molecule Inhibitors, Nano-particles and Nano-bodies" (2021). Molecular Medicine Faculty Publications. 908.