Featured Research

from universities, journals, and other organizations

Molecules 'light up' Alzheimer's roots

Date:
July 14, 2011
Source:
Rice University
Summary:
A breakthrough in sensing could make finding signs of Alzheimer's disease nearly as simple as switching on a light. The new technique should help researchers design better medications to treat the devastating disease.

Amyloid fibrils like those magnified here 12,000 times are thought to be the cause of plaques in the brains of Alzheimer's disease patients. Rice University researchers have created a metallic molecule that becomes strongly photoluminescent when it attaches to fibrils.
Credit: Nathan Cook/Rice University

A breakthrough in sensing at Rice University could make finding signs of Alzheimer's disease nearly as simple as switching on a light.

Related Articles


The technique reported in the Journal of the American Chemical Society should help researchers design better medications to treat the devastating disease.

The lab of Rice bioengineer Angel Martí is testing metallic molecules that naturally attach themselves to a collection of beta amyloid proteins called fibrils, which form plaques in the brains of Alzheimer's sufferers. When the molecules, complexes of dipyridophenazine ruthenium, latch onto amyloid fibrils, their photoluminescence increases 50-fold.

The large increase in fluorescence may be an alternative to molecules currently used to study amyloid fibrils, which researchers believe form when misfolded proteins begin to aggregate. Researchers use changes in fluorescence to characterize the protein transition from disordered monomers to aggregated structures.

Nathan Cook, a former Houston high school teacher and now a Rice graduate student and lead author of the new paper, began studying beta amyloids when he joined Martí's lab after taking a Nanotechnology for Teachers course taught by Rice Dean of Undergraduates and Professor of Chemistry John Hutchinson. Cook's goal was to find a way to dissolve amyloid fibrils in Alzheimer's patients.

But the Colorado native's research led him down a different path when he realized the ruthenium complexes, the subject of much study in Martí's group, had a distinctive ability to luminesce when combined in a solution with amyloid fibrils.

Such fibrils are simple to make in the lab, he said. Molecules of beta amyloid naturally aggregate in a solution, as they appear to do in the brain. Ruthenium-based molecules added to the amyloid monomers do not fluoresce, Cook said. But once the amyloids begin to aggregate into fibrils that resemble "microscopic strands of spaghetti," hydrophobic parts of the metal complex are naturally drawn to them. "The microenvironment around the aggregated peptide changes and flips the switch" that allows the metallic complexes to light up when excited by a spectroscope, he said.

Thioflavin T (ThT) dyes are the standard sensors for detecting amyloid fibrils and work much the same way, Marti said. But ThT has a disadvantage because it fluoresces when excited at 440 nanometers and emits light at 480 nanometers -- a 40-nanometer window.

That gap between excitation and emission wavelengths is known as the Stokes shift. "In the case of our metal complexes, the Stokes is 180 nanometers," said Martí, an assistant professor of chemistry and bioengineering. "We excite at 440 and detect in almost the near-infrared range, at 620 nanometers.

"That's an advantage when we want to screen drugs to retard the growth of amyloid fibrils," he said. "Some of these drugs are also fluorescent and can obscure the fluorescence of ThT, making assays unreliable."

Cook also exploited the metallic's long-lived fluorescence by "time gating" spectroscopic assays. "We specifically took the values only from 300 to 700 nanoseconds after excitation," he said. "At that point, all of the fluorescent media have pretty much disappeared, except for ours. The exciting part of this experiment is that traditional probes primarily measure fluorescence in two dimensions: intensity and wavelength. We have demonstrated that we can add a third dimension -- time -- to enhance the resolution of a fluorescent assay."

The researchers said their complexes could be fitting partners in a new technique called fluorescence lifetime imaging microscopy, which discriminates microenvironments based on the length of a particle's fluorescence rather than its wavelength.

Cook's goal remains the same: to treat Alzheimer's -- and possibly such other diseases as Parkinson's -- through the technique. He sees a path forward that may combine the ruthenium complex's ability to target fibrils and other molecules' potential to dissolve them in the brain.

"That's something we are actively trying to target," Martí said.

Co-authors of the paper are recent Rice graduate Veronica Torres and Disha Jain, a former postdoctoral researcher in Martí's lab.

The Welch Foundation supported the research.


Story Source:

The above story is based on materials provided by Rice University. Note: Materials may be edited for content and length.


Journal Reference:

  1. Nathan P. Cook, Veronica Torres, Disha Jain, Angel A. Martí. Sensing Amyloid-β Aggregation Using Luminescent Dipyridophenazine Ruthenium(II) Complexes. Journal of the American Chemical Society, 2011; 110630081548016 DOI: 10.1021/ja204656r

Cite This Page:

Rice University. "Molecules 'light up' Alzheimer's roots." ScienceDaily. ScienceDaily, 14 July 2011. <www.sciencedaily.com/releases/2011/07/110713121428.htm>.
Rice University. (2011, July 14). Molecules 'light up' Alzheimer's roots. ScienceDaily. Retrieved January 24, 2015 from www.sciencedaily.com/releases/2011/07/110713121428.htm
Rice University. "Molecules 'light up' Alzheimer's roots." ScienceDaily. www.sciencedaily.com/releases/2011/07/110713121428.htm (accessed January 24, 2015).

Share This


More From ScienceDaily



More Mind & Brain News

Saturday, January 24, 2015

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Smart Wristband to Shock Away Bad Habits

Smart Wristband to Shock Away Bad Habits

Reuters - Innovations Video Online (Jan. 23, 2015) — A Boston start-up is developing a wristband they say will help users break bad habits by jolting them with an electric shock. Ben Gruber reports. Video provided by Reuters
Powered by NewsLook.com
Amazing Technology Allows Blind Mother to See Her Newborn Son

Amazing Technology Allows Blind Mother to See Her Newborn Son

RightThisMinute (Jan. 23, 2015) — Not only is Kathy seeing her newborn son for the first time, but this is actually the first time she has ever seen a baby. Kathy and her sister, Yvonne, have been legally blind since childhood, but thanks to an amazing new technology, eSight glasses, which gives those who are legally blind the ability to see, she got the chance to see the birth of her son. It&apos;s an incredible moment and an even better story. Video provided by RightThisMinute
Powered by NewsLook.com
One Dose, Then Surgery to Test Tumor Drugs Fast

One Dose, Then Surgery to Test Tumor Drugs Fast

AP (Jan. 23, 2015) — A Phoenix hospital is experimenting with a faster way to test much needed medications for deadly brain tumors. Patients get a single dose of a potential drug, and hours later have their tumor removed to see if the drug had any affect. (Jan. 23) Video provided by AP
Powered by NewsLook.com
The Best Bedtime Rituals For a Good Night's Sleep

The Best Bedtime Rituals For a Good Night's Sleep

Buzz60 (Jan. 22, 2015) — What you do before bed can effect how well you sleep. TC Newman (@PurpleTCNewman) has bedtime rituals to induce the best night&apos;s sleep. Video provided by Buzz60
Powered by NewsLook.com

Search ScienceDaily

Number of stories in archives: 140,361

Find with keyword(s):
 
Enter a keyword or phrase to search ScienceDaily for related topics and research stories.

Save/Print:
Share:  

Breaking News:

Strange & Offbeat Stories

 

Health & Medicine

Mind & Brain

Living & Well

In Other News

... from NewsDaily.com

Science News

Health News

Environment News

Technology News



Save/Print:
Share:  

Free Subscriptions


Get the latest science news with ScienceDaily's free email newsletters, updated daily and weekly. Or view hourly updated newsfeeds in your RSS reader:

Get Social & Mobile


Keep up to date with the latest news from ScienceDaily via social networks and mobile apps:

Have Feedback?


Tell us what you think of ScienceDaily -- we welcome both positive and negative comments. Have any problems using the site? Questions?
Mobile iPhone Android Web
Follow Facebook Twitter Google+
Subscribe RSS Feeds Email Newsletters
Latest Headlines Health & Medicine Mind & Brain Space & Time Matter & Energy Computers & Math Plants & Animals Earth & Climate Fossils & Ruins