Featured Research

from universities, journals, and other organizations

First highly sensitive, small molecule fluorescence probe to evaluate risk, monitor progression of Parkinson's disease

Date:
March 3, 2014
Source:
National University of Singapore
Summary:
The first two-photon, small molecule fluorogenic probe that can serve as a useful tool for the rapid assessment of an individual’s potential risk for Parkinson’s disease has been developed by scientists. The probe can detect with high precision the activity of Monoamine Oxidase B (MAO-B), an enzyme that is found in elevated levels in patients with Parkinson’s disease. This innovation paves the way for the development of less costly non-invasive technologies and devices to help monitor the risk and progression of Parkinson’s disease.

A team of researchers from National University of Singapore (NUS) have created the first two-photon, small molecule fluorogenic probe that can serve as a useful tool for the rapid assessment of an individual's potential risk for Parkinson's disease. The highly sensitive fluorescence probe can detect with high precision the activity of Monoamine Oxidase B (MAO-B), an enzyme that is found in elevated levels in patients with Parkinson's disease. This innovation paves the way for the development of less costly non-invasive technologies and devices to help monitor the risk and progression of Parkinson's disease.

The study is co-led by Professor Yao Shao Qin from the Department of Chemistry, Faculty of Science at NUS and Associate Professor Lim Kah Leong, from the National Neuroscience Institute, Singapore and also the Department of Physiology at NUS Yong Loo Lin School of Medicine. The findings are published in Nature Communications journal this month.

Enabling highly sensitive, specific and real-time imaging of MAO-B activities

Monoamine oxidases (MAOs) are enzymes that are found mainly in the human brain. Its two isoforms -- MAO-A and MAO-B -- work together to help maintain the balance of neurotransmitters in the brain. But when the enzymes are over-activated, the brain produces an excessive level of neurotoxic byproducts, causing neuronal dysfunctions that lead to psychiatric disorders and neurodegenerative diseases. In the case of Parkinson's disease, it is found that the expression of MAO-B, but not MAO-A, is significantly enhanced in the brain of patients and increases with age.

The high MAO-B activity consistently observed in patients with Parkinson's disease has been proposed as a biomarker, but there has been a lack of suitable small molecule probes for MAO-B specific detection in live cells and tissues. Some of the existing fluorescence-based MAO-B probes require the addition of activating reagents, which can affect the properties of the enzymes and reduce the accuracy of detection, while some others are unable to distinguish precisely between MAO-B and the closely related MAO-A.

The small molecule probe designed and synthesised by the NUS team addresses these inadequacies of existing probes. Their probe is highly sensitive and can detect MAO-B specifically with greater precision. The fluorescence label on the probe also allows it to be detected via high-resolution imaging techniques in tissues and organs at depths of up to one millimeter, which enables researchers to effectively monitor the in vivo enzymatic activities of MAO-B in living systems. These were all not possible previously with the existing MAO probes.

MAO-B as a biomarker for Parkinson's disease

The study also found that in patients with Parkinson's disease, MAO-B activities are present only in human B-lymphocytes (a type of white blood cell), but not in fibroblasts (cells typically found in connective tissues).

"This suggests that MAO-B activity in peripheral blood cells of a patient might serve as an accessible and economical biomarker to evaluate the potential risk of an individual for this disease," said Assoc Prof Lim. Presently there is no reliable biomarker for Parkinson's disease, either at the diseased or preclinical state, except for dopamine-based PET imaging, which is costly and requires highly specialised skills to perform.

"The probe may potentially be useful to monitor patient's response to medication," said Associate Professor Louis Tan, Senior Consultant, Department of Neurology at the National Neuroscience Institute, whose team has recently shown in a separate study that long term use of a MAO-B inhibitor reduces the progression of early Parkinson's disease.

The probe also has no apparent toxicity in most mammalian cells, so it can be used to monitor in vivo MAO-B activities during various stages of the disease. As such, the probe can also become a useful tool to understand how Parkinson's disease progresses as well as for drug development.

"Our findings for this study provide important starting points for using small molecule imaging techniques to explore MAO-B further at the organism level, and in fact, opens up future prospects for non-invasive imaging-based diagnostic applications," said Dr Li Lin, the first author of the paper and a post-doctoral fellow in Prof Yao's lab.

Next steps

The NUS research team intends to further their research on the probe. One of their immediate priorities is to validate the effectiveness of their probe in detecting MAO-B in a larger pool of patient samples, with an aim of eventually developing the probe into a commercial test kit to monitor the progression of Parkinson's disease.

The team also recently obtained a grant from the National Medical Research Council in Singapore to pursue a study using the probe to examine the relationship between key Parkinson's disease-linked genes and MAO-B expression and activity to further understand the causes of the disease and illuminate the role of MAO-B in this.


Story Source:

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


Journal Reference:

  1. Lin Li, Cheng-Wu Zhang, Grace Y. J. Chen, Biwei Zhu, Chou Chai, Qing-Hua Xu, Eng-King Tan, Qing Zhu, Kah-Leong Lim, Shao Q. Yao. A sensitive two-photon probe to selectively detect monoamine oxidase B activity in Parkinson’s disease models. Nature Communications, 2014; 5 DOI: 10.1038/ncomms4276

Cite This Page:

National University of Singapore. "First highly sensitive, small molecule fluorescence probe to evaluate risk, monitor progression of Parkinson's disease." ScienceDaily. ScienceDaily, 3 March 2014. <www.sciencedaily.com/releases/2014/03/140303083549.htm>.
National University of Singapore. (2014, March 3). First highly sensitive, small molecule fluorescence probe to evaluate risk, monitor progression of Parkinson's disease. ScienceDaily. Retrieved July 31, 2014 from www.sciencedaily.com/releases/2014/03/140303083549.htm
National University of Singapore. "First highly sensitive, small molecule fluorescence probe to evaluate risk, monitor progression of Parkinson's disease." ScienceDaily. www.sciencedaily.com/releases/2014/03/140303083549.htm (accessed July 31, 2014).

Share This




More Health & Medicine News

Thursday, July 31, 2014

Featured Research

from universities, journals, and other organizations


Featured Videos

from AP, Reuters, AFP, and other news services

Health Insurers' Profits Slide

Health Insurers' Profits Slide

Reuters - Business Video Online (July 30, 2014) Obamacare-related costs were said to be behind the profit plunge at Wellpoint and Humana, but Wellpoint sees the new exchanges boosting its earnings for the full year. Fred Katayama reports. Video provided by Reuters
Powered by NewsLook.com
Concern Grows Over Worsening Ebola Crisis

Concern Grows Over Worsening Ebola Crisis

AFP (July 30, 2014) Pan-African airline ASKY has suspended all flights to and from the capitals of Liberia and Sierra Leone amid the worsening Ebola health crisis, which has so far caused 672 deaths in Guinea, Liberia and Sierra Leone. Duration: 00:43 Video provided by AFP
Powered by NewsLook.com
At Least 20 Chikungunya Cases in New Jersey

At Least 20 Chikungunya Cases in New Jersey

AP (July 30, 2014) At least 20 New Jersey residents have tested positive for chikungunya, a mosquito-borne virus that has spread through the Caribbean. (July 30) Video provided by AP
Powered by NewsLook.com
Xtreme Eating: Your Daily Caloric Intake All On One Plate

Xtreme Eating: Your Daily Caloric Intake All On One Plate

Newsy (July 30, 2014) The Center for Science in the Public Interest released its 2014 list of single meals with whopping calorie counts. Video provided by Newsy
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:
from the past week

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