Nanoimaging for protein misfolding and related diseases.
Misfolding and aggregation of proteins is a common thread linking a number of important human health problems. The misfolded and aggregated proteins are inducers of cellular stress and activators of immunity in neurodegenerative diseases. They might possess clear cytotoxic properties, being responsible for the dysfunction and loss of cells in the affected organs. Despite the crucial importance of protein misfolding and abnormal interactions, very little is currently known about the molecular mechanism underlying these processes. Factors that lead to protein misfolding and aggregation in vitro are poorly understood, not to mention the complexities involved in the formation of protein nanoparticles with different morphologies (e.g., the nanopores) in vivo. A better understanding of the molecular mechanisms of misfolding and aggregation might facilitate development of the rational approaches to prevent pathologies mediated by protein misfolding. The conventional tools currently available to researchers can only provide an averaged picture of a living system, whereas much of the subtle or short-lived information is lost. We believe that the existing and emerging nanotools might help solving these problems by opening the entirely novel pathways for the development of early diagnostic and therapeutic approaches. This article summarizes recent advances of the nanoscience in detection and characterization of misfolded protein conformations. Based on these findings, we outline our view on the nanoscience development towards identification intracellular nanomachines and/or multicomponent complexes critically involved in protein misfolding.
Lyubchenko
Yuri L
YL
Department of Pharmaceutical Sciences, University of Nebraska Medical Center, Omaha, Nebraska 68198-6025, USA. ylyubchenko@unmc.edu
Sherman
Simon
S
Shlyakhtenko
Luda S
LS
Uversky
Vladimir N
VN
D000682:Amyloid / Q000737:chemistry; D000818:Animals; D006801:Humans; D021621:Imaging, Three-Dimensional; D008958:Models, Molecular; D036103:Nanotechnology / Q000379:methods*; D019636:Neurodegenerative Diseases / Q000378:metabolism / Q000503:physiopathology; D017510:Protein Folding; D011506:Proteins / Q000032:analysis / Q000737:chemistry* / Q000378:metabolism
D000682:Amyloid; D011506:Proteins