Glial Imaging—Amid Slow Progress EU Project Takes Up Challenge ALZFORUM — Volkswagen Fox-EU

21 Апр 2015 | Author: | Комментарии к записи Glial Imaging—Amid Slow Progress EU Project Takes Up Challenge ALZFORUM — Volkswagen Fox-EU отключены

Volkswagen Fox-EU


How would you like to

26 Mar 2013

Calls for functional emanated loud and clear the 3rd Venusberg Meeting on Neuroinflammation, 28 February-2 March 2013 at the Center, University of Bonn, Markers for brain-resident microglia and macrophages, that is. Despite interest in the role of immune in Alzheimer’s and related diseases, remain hamstrung by difficulties these cells and figuring out they do in disease. Developing for in-vivo imaging has proven vexing. In Venusberg, members of of Neuroinflammation in Neurodegenerative Diseases a European consortium seeking targets for diagnostic and therapeutic reported on potential new tracers. researchers lamented that all bind the same target, a transporter. INMiND principal Andreas Jacobs . Westfälische Münster, Germany, told that tracers for other targets, including enzymes and surface receptors, are being but no leading contender has yet to emerge.

For decades, researchers have glia in vivo by imaging a transporter in the outer mitochondrial PK11195, a ligand developed in the 1980s, binds this with high affinity and has used to image microglia in a of human conditions, including (see ARF related news ), stroke, viral encephalitis, and recently to identify inflammation in who have suffered traumatic injury (see Ramlackhansingh et al. ). However, the ligand has its drawbacks. For it tells nothing about the of microglia, or why they are active, INMiND investigator David . Imperial College London, PK11195 lacks specificity, penetrates the brain, and has a weak ratio.

Against this researchers in Europe conceived of to develop probes for microglial and study the basic mechanisms underscore neuroinflammation. The project from a Diagnostic Molecular (DiMI) project the EU funded 2005 to 2010. When ended, Jacobs, together about 50 of the neuroscience partners DiMI, applied for fresh EU The idea was to focus on the microglial of neuroinflammation, Jacobs told

INMiND comprises a collaboration 20 academic partners in Europe, one in and seven small to medium enterprises, said Jacobs. its Seventh Framework Programme the EU funds the project to the tune of million over five An additional €8 million from the partner academic in 12 countries.

Jacobs told that INMiND will the earliest stages of disease, on familial Alzheimer’s, familial disease, and on patients with clinical impairment who test for brain amyloid and are at great of progressing to Alzheimer’s dementia Okello et al. 2009 ). INMiND are planning a clinical trial to MCI patients while following activation with molecular “We want to see if we can modify load, postpone AD, and tell how are involved in that process,” Jacobs. The imaging agent has yet to be he said.

Therein lies the challenge. imaging agents are emerging so slowly. Researchers in France, INMiND investigator Bertrand at the Atomic Energy Commission in have developed a new range of ligands that have profiles than PK11195, but also have problems, notably binding only to people who have certain isoforms (see ARF related story ). That complicates said Brooks, because it populations into high and low Distinguishing people with AD, for from controls then problematic, he said, because controls take up more of the than low-binder AD patients. new TSPO ligands, including and the DAA family of ligands (see et al. 2011 ) exhibit this binding.

Brooks noted GE-180, a TSPO ligand developed by GE Healthcare, where worked previously, shows a binding profile than but so far has only been tested in models. Uptake and retention of in brain areas that TSPO compare well that of other ligands, but it to be cleared more rapidly low-binding regions, improving its ratio. How this ligand to TSPO isoforms remains to be

Volkswagen Fox-EU

Researchers at the Venusberg meeting why TSPO continues to be a focus for development. In summing up the meeting, Perry . University of Southampton, the community to come up with better. Some researchers cell surface markers, than a mitochondrial transporter, be more thoroughly investigated. noted that new research at the meeting has turned up a suite of markers (see ARF related story ) that offer hunting ground for new ligands.

In vein, Olga Garaschuk . of Tübingen, Germany, suggested lectins. She reported that B4 binds to microglia when into the brains of transgenic (Eichhoff et al. 2011 ). IB4 binding with green fluorescent expression driven by a microglial It also bound to blood but Garaschuk did not see that as a major since vessels and microglia are distinguished. Tomato lectin was better (see image lighting up tiny microglial that IB4 missed (see Schwendele et al. 2012 ).

Lectins Label Microglia

594-conjugated tomato lectin labels microglia expressing green fluorescent protein Image courtesy of Bianca and Olga Garaschuk, University of

How do lectins work? They high affinity for sugar which are rich on microglia. lectin binds N-acetylglucosamine while α-galactose-rich proteins IB4. Garaschuk noted unlike astroglial marker 101 that induced long-term when injected into the (for a review, see Garaschuk, ), tomato lectin seems to biological activity. Microglia appear fully motile they bind the ligand.

Brooks noted other targets that might useful, including cannabinoid and receptors. Jacobs said receptors often make targets, suggesting instead imaging arginase activity prove useful, as activated upregulate this enzyme. The here would be to make a that can be metabolized by arginase a compound that gets in the cell. Tom Fagan.

Volkswagen Fox-EU


Tagged as:

Other articles of the category "Fox":

Our partners
Follow us
Contact us
Our contacts

Born in the USSR

About this site

For all questions about advertising, please contact listed on the site.

Volkswagen all cars catalog with specifications, pictures, ratings, reviews and discusssions about cars Volkswagen.