Multiple Function Fluorescein Probe Performs Metal Chelation, Disaggregation, and Modulation of Aggregated Aβ and Aβ-Cu Complex

ACS Chemical Neuroscience
Balakrishnan MuthurajParameswar K Iyer

Abstract

An exceptional probe comprising indole-3-carboxaldehyde fluorescein hydrazone (FI) performs multiple tasks, namely, disaggregating amyloid β (Aβ) aggregates in different biomarker environments such as cerebrospinal fluid (CSF), Aβ1-40 fibrils, β-amyloid lysozyme aggregates (LA), and U87 MG human astrocyte cells. Additionally, the probe FI binds with Cu(2+) ions selectively, disrupts the Aβ aggregates that vary from few nanometers to micrometers, and prevents their reaggregation, thereby performing disaggregation and modulation of amyloid-β in the presence as well as absence of Cu(2+) ion. The excellent selectivity of probe FI for Cu(2+) was effectively utilized to modulate the assembly of metal-induced Aβ aggregates by metal chelation with the "turn-on" fluorescence via spirolactam ring opening of FI as well as the metal-free Aβ fibrils by noncovalent interactions. These results confirm that FI has exceptional ability to perform multifaceted tasks such as metal chelation in intracellular conditions using Aβ lysozyme aggregates in cellular environments by the disruption of β-sheet rich Aβ fibrils into disaggregated forms. Subsequently, it was confirmed that FI had the ability to cross the blood-brain barrier and it also modulate...Continue Reading

References

Dec 1, 1991·The Journal of Cell Biology·L L RubinJ Morales
Jun 1, 1991·Lancet·D R Crapper McLachlanD F Andrews
Mar 1, 1991·Trends in Pharmacological Sciences·W Kalow
Apr 22, 1999·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·L GaleazziS Giunta
Aug 7, 1999·The Journal of Biological Chemistry·R A ChernyA I Bush
Oct 6, 2000·Amyloid : the International Journal of Experimental and Clinical Investigation : the Official Journal of the International Society of Amyloidosis·S GiuntaL Galeazzi
Jan 15, 2003·Biochemistry·Melanie R Nilsson, Christopher M Dobson
Mar 21, 2003·The Journal of Biological Chemistry·Tadato BanYuji Goto
Sep 25, 2003·Lancet Neurology·Kaj Blennow, Harald Hampel
Jan 14, 2004·Biochemistry·Craig S AtwoodAshley I Bush
Nov 16, 2004·Journal of Inorganic Biochemistry·Ayesha KhanChristopher Exley
Apr 6, 2005·Biochemistry·Jesse W KarrVeronika A Szalai
Apr 6, 2006·The Journal of Biological Chemistry·David P SmithKevin J Barnham
Sep 26, 2006·Drug Discovery Today·Yan-Jiang WangXin-Fu Zhou
Apr 17, 2007·Biochimica Et Biophysica Acta·Danielle G SmithKevin J Barnham
Jun 7, 2007·The Journal of Pharmacology and Experimental Therapeutics·Gracious R RossHamid I Akbarali
Jul 3, 2007·Cellular and Molecular Life Sciences : CMLS·X ZhuG Perry
Jul 16, 2008·Archives of Neurology·Joshua R SteinermanYaakov Stern
Aug 30, 2008·The Journal of Biological Chemistry·Wei-hui WuYan-mei Li
Oct 11, 2008·The Journal of Biological Chemistry·Robin RoychaudhuriDavid B Teplow
Oct 29, 2008·Journal of the American Chemical Society·Celia Cabaleiro-LagoSara Linse
Nov 13, 2008·Dalton Transactions : an International Journal of Inorganic Chemistry·Lauren E ScottChris Orvig
Jan 15, 2009·Journal of Neurochemistry·Peter J CrouchAnthony R White
Mar 27, 2009·Dalton Transactions : an International Journal of Inorganic Chemistry·Peter Faller, Christelle Hureau
Mar 31, 2009·Angewandte Chemie·Roland Jakob-Roetne, Helmut Jacobsen
Aug 20, 2009·Chemical Society Reviews·Arvi Rauk
Nov 3, 2009·Journal of the American Chemical Society·Sarmad S HindoMi Hee Lim
Nov 11, 2009·Proceedings of the National Academy of Sciences of the United States of America·Kazuhiro TakumaShirley Shidu Yan
Feb 17, 2010·Nature Reviews. Neurology·Kaj BlennowHenrik Zetterberg
Feb 19, 2010·Journal of Alzheimer's Disease : JAD·Noel G FauxAshley I Bush
Apr 7, 2010·Biosensors & Bioelectronics·Olaf J RolinskiDavid J S Birch
May 7, 2010·Progress in Neurobiology·James A Duce, Ashley I Bush
Nov 10, 2010·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Bruno AliesPeter Faller
Dec 7, 2010·Proceedings of the National Academy of Sciences of the United States of America·Jung-Suk ChoiMi Hee Lim
Dec 15, 2010·Journal of the American Chemical Society·Debajyoti Pramanik, Somdatta Ghosh Dey
Jan 5, 2011·International Journal of Alzheimer's Disease·Joseph J BraymerMi Hee Lim

❮ Previous
Next ❯

Citations

Jun 30, 2016·ACS Chemical Neuroscience·K RajasekharT Govindaraju
Apr 2, 2016·Scientific Reports·K RajasekharT Govindaraju
Jan 5, 2019·Dalton Transactions : an International Journal of Inorganic Chemistry·Aniruddha DasShyam Biswas
Aug 5, 2017·ACS Chemical Neuroscience·Paulina GonzalezKayla N Green
May 30, 2019·ACS Chemical Neuroscience·Sourav SamantaThimmaiah Govindaraju

❮ Previous
Next ❯

Related Concepts

Related Feeds

Blood Brain Barrier

The blood brain barrier is a border that separates blood from cerebrospinal fluid. Discover the latest search on this highly selective semipermeable membrane here.

Blood Brain Barrier Regulation in Health & Disease

The blood brain barrier is essential in regulating the movement of molecules and substances in and out of the brain. Disruption to the blood brain barrier and changes in permeability allow pathogens and inflammatory molecules to cross the barrier and may play a part in the pathogenesis of neurodegenerative disorders. Here is the latest research in this field.

Bacterial Cell Wall Structure

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.

CSF & Lymphatic System

This feed focuses on Cerebral Spinal Fluid (CSF) and the lymphatic system. Discover the latest papers using imaging techniques to track CSF outflow into the lymphatic system in animal models.

Astrocytes

Astrocytes are glial cells that support the blood-brain barrier, facilitate neurotransmission, provide nutrients to neurons, and help repair damaged nervous tissues. Here is the latest research.

Bacterial Cell Wall Structure (ASM)

Bacterial cell walls are made of peptidoglycan (also called murein), which is made from polysaccharide chains cross-linked by unusual peptides containing D-amino acids. Here is the latest research on bacterial cell wall structures.

Astrocytes & Amyloid

Astrocytes are thought to play a role in amyloid production and have been implicated in neurodegenerative diseases such as Alzheimer’s disease. Here is the latest research on the relationship between astrocytes and amyloid.

Blood Brain Barrier Chips

The blood brain barrier (BBB) is comprised of endothelial cells that regulate the influx and outflux of plasma concentrations. Lab-on-a-chip devices allow scientists to model diseases and mechanisms such as the passage of therapeutic antibodies across the BBB. Discover the latest research on BBB chips here.