title: Detection, inhibition and disintegration of amyloid fibrils: the role of optical probes and macrocyclic receptors.
abstract: Amyloid fibrils are formed by the aberrant aggregation of proteins into highly ordered β-sheet structures and are believed to be the root cause of several neurodegenerative diseases such as Alzheimer's disease, Parkinson's disease, Prion diseases, etc. and have been the subject of extensive biochemical, biophysical and clinical studies. Developing methods for the early detection of fibril formation using optical spectroscopic techniques and inhibition/disintegration of amyloid fibrils/plaques by introducing small molecules have been a major challenge to establish a clinically facile therapeutic intervention to combat these neurodegenerative diseases. This feature article provides an account of the recent reports from different research groups, including ours, on the optical detection, and inhibition/disintegration of mature fibrils using fluorescent probes and macrocyclic hosts such as cucurbiturils, calixarenes and cyclodextrins. Site specific or spectrally distinct fluorescence emission from a large number of fluorophores in a broad spectral region has been used to detect the fibrillation of different proteins/peptides, mainly insulin, α-synuclein, transthyretin, barstar, lysozyme, Aβ40 peptide, etc. On the one hand, while macrocyclic receptors modify the inter-protein interactions through molecular recognition of amino acid residues leading to the inhibition of amyloid fibrillation, on the other hand, one of the cavitands, p-sulfonatocalixarenes, has been demonstrated to cause the disintegration of mature fibrils, effectively through surface charge interactions, which destabilize the extended fibrillar structure into soluble or fine particles. Beneficially, the presence of extrinsic p-sulfonatocalix[4/6]arenes did not introduce any additional toxicity to the cell viability, which advocates its potential utility as a therapeutic for amyloidosis.
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India. bkac@barc.gov.in jyotim@barc.gov.in and Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India.
authors.forename: Achikanath C
authors.initials: AC
authors.lastname: Bhasikuttan
authors.affiliation: Radiation & Photochemistry Division, Bhabha Atomic Research Centre, Mumbai 400085, India. bkac@barc.gov.in jyotim@barc.gov.in and Homi Bhabha National Institute, Training School Complex, Anushaktinagar, Mumbai 400094, India.
authors.forename: Jyotirmayee
authors.identifier: http://orcid.org/0000-0002-2018-4906
authors.initials: J
authors.lastname: Mohanty
mesh_terms: D000682:Amyloid / Q000032:analysis* / Q000037:antagonists & inhibitors*; D002470:Cell Survival; D005453:Fluorescence; D005456:Fluorescent Dyes / Q000737:chemistry*; D006801:Humans; D047028:Macrocyclic Compounds / Q000737:chemistry*; D061848:Optical Imaging; D013050:Spectrometry, Fluorescence
chemical_list: D000682:Amyloid; D005456:Fluorescent Dyes; D047028:Macrocyclic Compounds