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What are the toxic ones?

07.11.2013 14:47

The research field of Alzheimer’s disease debates already a long time about the different toxicity levels of the amyloid beta peptide and which is more neuro-toxic. Soluble Abeta peptides are known to be involved in the etiology of this devastating disease, which will affect more and more people in our ageing population.

NeuroProof has developed a phenotypic screening method on the base of its MEA-chip platform.  Results from multiple in-house projects and costumer projects overwhelmingly show that the monomeric isoforms of this peptide specifically are the most potent form significantly affecting our neuronal networks.

From a phenotypic and functional point of view this paves the way for therapeutic intervention, which rescue neuro-functional effects of monomeric ABeta peptides.

This and other novel assays the team of NeuroProof will discuss with its partners at the upcoming SfN meeting in San Diego. Visit NeuroProof at booth 517.

Arvid Carlsson

13.03.2013 11:15

I recently found this quotation of Nobel Prize Winner Arvid Carlsson and thought it describes best what we are doing at NeuroProof:

"I think there will be a shift away from purely molecular aspects of chemical transmission to include neuro-circuits of intact systems on both the microscopic and the macroscopic level. It is very important to grasp a number of tissue patterns using modern computer techniques. I believe that we will awake from treating the brain as a chemical factory and look at it more as a extremely complicated survival machine. This is not to say that modern techniques are not very useful, but it is even better to work together with both the new imaging techniques and advanced computer dependent statistics involving pattern recognition. Those studies will probably prove extremely useful and very much help to bridge the gap between animal and human observations. The future looks very bright indeed. I am positive that lots of important things will happen and that many people suffering from mental and neurological disorders shall benefit greatly from these developments!"
 
Arvid Carlsson

 

This is in essence what we are doing in modern phenotypic screening. It is a different wording for this new wave in drug discovery. Pattern Recognition is the new quality in these techniques. I think two points are important to mention: First, human thinking is strongly limited in estimation of probabilities. In daily life we often see strange assessments for example for life risks. Pattern Recognition algorithms can manage probabilities much more precise than humans.  Second, high dimensional data spaces are not suited for our thinking. Pattern Recognition were developed for high dimensional problems. Therefore we need tools which help us to navigate in this complex, e.g. high-dimensional, and vague, e.g. noisy, world.

Best,

Olaf

 

New Substance Database

13.03.2013 11:14

Read our new Substance Database, containing more than 100 Substances.

Superpotent [Dmt¹] dermorphin tetrapeptides

13.03.2013 00:00

Abstract

Novel dermorphin tetrapeptides are described in which Tyr(1) is replaced by Dmt(1), where d-Ala(2) and Gly(4) are N-methylated, and where Phe(3)-Gly(4) residue is substituted by the constrained Aba(3)-Gly(4) peptidomimetic. Most of these peptidic ligands displayed binding affinities in the nanomolar range for both μ- and δ-opioid receptors but no detectable affinity for the κ-opioid receptor. Measurements of cAMP accumulation, phosphorylation of extracellular signal-regulated kinase (ERK1/2) in HEK293 cells stably expressing each of these receptors individually, and functional screening in primary neuronal cultures confirmed the potent agonistic properties of these peptides. The most potent ligand H-Dmt-NMe-d-Ala-Aba-Gly-NH(2) (BVD03) displayed mixed μ/δ opioid agonist properties with picomolar functional potencies. Functional electrophysiological in vitro assays using primary cortical and spinal cord networks showed that this analogue possessed electrophysiological similarity toward gabapentin and sufentanil, which makes it an interesting candidate for further study as an analgesic for neuropathic pain.

2012