Researcher at Molecular Connections develop a Alzheimer disease Pathways Compendium for inclusion at the Alzforum

This Pathways Compendium provides an index of Alzheimer disease pathway models contributed by researchers and companies.

Probable Interaction Networks Involved in Pathology of Alzheimer Disease: Predicting Targets and Therapeutic Agents - NetPro™ based Study. Developed by researchers at Molecular Connections Private Limited, an in silico discovery services company. Users can click on a specific node (molecule) to get information on all interactions of the molecule in the given network. Click on the interaction arrows for information on the specific interaction.

The Alzheimer Research Forum is a Pioneering Biomedical Web Community. Founded 13 years ago when the Web was still in its infancy, the "Alzforum" has more than 5,000 registered members and is familiar to most Alzheimer scientists in the world.


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Potatoes may hold key to Alzheimer's treatment

A virus that commonly infects potatoes bears a striking resemblance to one of the key proteins implicated in Alzheimer's disease (AD), and researchers have used that to develop antibodies that may slow or prevent the onset of AD.

Studies in mice have demonstrated that vaccinations with the amyloid beta protein (believed to be a major AD contributor) to produce AD antibodies can slow disease progression and improve cognitive function, possibly by promoting the destruction of amyloid plaques. Some early human trials have likewise been promising, but had to be halted due to the risk of autoimmune encephalitis.

One way to make Alzheimer's vaccinations safer would be to use a closely-related, but not human, protein as the vaccine, much like cowpox virus is used for smallpox immunizations.

In the August 15 Journal of Biological Chemistry, Robert Friedland and colleagues used this concept on an amyloid-like protein found in potato virus (PVY). They injected PVY into mice followed by monthly boosters for four months. The researchers found that the mice produced strong levels of antibodies that could attach to amyloid beta protein both in both solution and in tissue samples of Alzheimer's patients. And although the levels were lower, mice also developed AD antibodies if given injections of PVY-infected potato leaf as opposed to purified PVY.

Friedland and colleagues note that potato virus is a fairly common infection that poses no risk to humans (many people have probably eaten PVY infected potatoes). While tests of PVY antibodies will ultimately determine how useful they can be, they may be a promising lead to treating this debilitating disease.

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Researchers create molecule that nudges nerve stem cells to mature

The last time i blogged on stem cells it was rather about a challenge in Fresh hurdle for stem cell hunt, but this time its more on a positive note and fairly quite an interesting and welcome news... a SERENDIPITY!

Inspired by a chance discovery during another experiment, researchers at UT Southwestern Medical Center have created a small molecule that stimulates nerve stem cells to begin maturing into nerve cells in culture.

"This provides a critical starting point for neuro-regenerative medicine and brain cancer chemotherapy," said Dr. Jenny Hsieh, assistant professor of molecular biology and senior author of the paper, Small-molecule activation of neuronal cell fate, Jay W Schneider, Zhengliang Gao, Shijie Li, Midhat Farooqi, Tie-Shan Tang, Ilya Bezprozvanny, Doug E Frantz, Jenny Hsieh
SUMMARY: We probed an epigenetic regulatory path from small molecule to neuronal gene activation. Isoxazole small molecules triggered robust neuronal differentiation in adult neural stem.
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Human-pathogen Protein Interactions Illuminated With Bioinformatics

Previously blogging on the how protein interactions play significant roles in various aspects of the structural and functional organization of the cell, and their elucidation sheds light on the molecular mechanisms of biological processes. Researchers Find that a Small Molecule Can Activate an Important Cancer Suppressor Gene. Here is another study where researchers have provided the first global analysis of human proteins interacting with viral proteins and proteins in other pathogens. The scientists examined experimental data for 190 different pathogens that comprise 10,477 interactions between human and pathogen proteins. This approach provides a highly detailed network map of human proteins interfacing with proteins in different pathogens. The network of interactions reveals possible key intervention points for the future development of therapeutics against infectious diseases.

"Infectious diseases result in millions of deaths each year. Although much effort has been directed towards the study of how infection by a pathogen causes disease in humans. We have to leverage the opportunity to compare protein interactions between human and pathogen proteins, from 190 different pathogens to provide important insights into the strategies used by pathogens to infect human cells."

"Previous studies have suggested that protein interaction networks have topologies that are resilient to attacks on random nodes but are susceptible to targeted attacks, for example on hubs. Our results provide a striking example of how pathogens may have evolved the ability to exploit the structure of interactions between human proteins in order to promote infection. This global study also suggests that many viruses share similar strategies to control the human cell cycle, regulate programmed cell death, and transport viral genetic material across the nuclear membrane in the human cell." said one of the investigators

The researchers paid particular attention to two networks of human proteins -- proteins that interact with at least two viral pathogens and proteins that interact with at least two bacterial pathogens. Gene Ontology (GO) terms computed for both sets of proteins provided key information on the functions of the different proteins. Some of the striking findings of the study included a clear demonstration that pathogens preferentially interact with two classes of human proteins referred to as hubs and bottlenecks. Hubs are popular proteins that interact with many other proteins in the human protein interaction network.

Bottlenecks are proteins that lie on many of the shortest paths in the network. Pathogens appear to maximize their likelihood of success by targeting these high-impact, influential proteins during infection. In many cases, human proteins that mediate pathogen effects are proteins that are known to be involved in cancer pathways, for example, the transcription factor STAT1 or the tumor suppressor protein TP53. This finding suggests interesting parallels between pathogen infection and cancer and opens up future areas for research.

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Scientists Identify Potential Alzheimer’s Drug Target

Researchers found that the thromboxane receptor, which is activated by isoprostanes, may be a new therapeutic target for Alzheimer’s disease (AD). Previous studies have shown that two isoprostane isoforms are know to be elevated in AD and AD-like diseases but not in other neurodegenerative diseases.

Investigators found that injection of one of these isoprostanes increased the number of amyloid plaques in a mouse model of AD. They further showed that activation of the thromboxane receptor increased levels of amyloid precursor protein (APP) and its cleavage products including those that form plaques. The thromboxane receptor also increased the stability of APP mRNA and this likely provides more substrate for amyloid production, according to the researchers.

The scientists also showed that thromboxane receptor antagonists reversed the effects of isoprostane injection in mice and also reduced plaque formation in Tg2576 mice that were not treated with isoprostane.

The researchers involved in this study were from the University of Pennsylvania School of Medicine and Temple University. The study is published in the April 30 issue of the Journal of Neuroscience.

Drug Target For The Most Potent Botulinum Neurotoxin Determined

Brookhaven Lab researchers Subramanyam Swaminathan, Desigan Kumaran and Richa Rawat.

"We have found a highly efficient inhibitor of botulinum neurotoxin type A - the most potent of seven neurotoxins produced by the bacterium Clostridium botulinum. This finding can lead to a very effective drug to stop the devastating effects of the toxin," said Dr. Subramanyam Swaminathan,

Botulinum neurotoxin -- responsible for the deadly food poisoning disease botulism and for the beneficial effects of smoothing out facial wrinkles - can also be used as a dreaded biological weapon. When ingested or inhaled, less than a billionth of an ounce can cause muscle paralysis and eventual death. Although experimental vaccines administered prior to exposure can inhibit the destructive action of this neurotoxin - the most deadly protein known to humans -- no effective pharmacological treatment exists. Scientists have now taken the first step toward designing an effective antidote to the most potent form of botulinum neurotoxin.

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British Team Finds Two Genes For Osteoporosis

British researchers have identified two common genetic mutations that increase the risk of osteoporosis and related bone fractures, according to a study released on Tuesday. These changes were present in 20 percent of the people studied and highlight the potential role of screening for the bone-thinning.

Talking about Osteoporosis, other related bone diseases affecting bone formation and repair. There has been increased interest both in academia and industry in tissue regeneration and working towards understanding the biological processes involved in self regeneration.

The key to success is in understanding basic developmental processes focused on tissue regeneration (including bone formation and repair). One such key resource researchers might be interested in, is Receptome – a knowledgebase of functional endogenous ligand-receptor pairs in developmental processes.

Few key applications areas are : to identify major mediators, roles in cellular processes, expression and role of specific cell surface receptors, multi-receptor pharmacology, identify high affinity ligands and activators, natural modulators of functional ligand-receptor pairs, critical signaling nodes, transcription factors, target genes, etc.

Tissue-specific blood stem cell line established from embryonic stem cells

A research team at the Umeå Center for Molecular Medicine (UCMM) in Sweden, led by Professor Leif Carlsson, has managed to specifically establish and isolate the tissue-specific stem cell that produces blood cells (blood stem cell) by using genetically modified embryonic stem cells.

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Nature News catches up on the state of gene therapy trials against blindness

Blogging already on the recent developments in Gene Therapy , This weekend two teams reported success in helping people to see again. Nature News catches up on the state of gene therapy trials against blindness due to Leber’s congenital amaurosis (LCA).

LCA, a rare inherited form of blindness. Patients with LCA have a genetic defect that affects the development of the light receptors in their eyes; typically they have poor vision at birth and are blind within three decades. Some 3,000 people are thought to be affected in the United States.

here are answers to some important questions that may arise like:

What sort of blindness do the new reports address?

Were the patients 'cured'?

How does it work?

What other treatments are being investigated for severe blindness?

Has gene therapy been trialled for blindness before?

for answers read

Beating heart tissue grown in lab

Talking about novel receptor genes expressed in human tissues. This morning's news featured, An international team of cell biologists has created heart tissue — complete with beat — in a test tube. The tissue culture contains three distinct cell types, each of which is important in functioning hearts, and is thus a step towards the advent of lab-grown heart-tissue transplants.

To day, research is considerably accelerated by the use of scientific knowledgebase and informatics tools which aid researchers significantly minimize time and effort spent on knowledge transfer across their teams and in scientific study. Thanks to such tools which supplement lab work and act as comprehensive repertoire that make optimal use of the plethora of data available in literature and centralize it as a searchable tool to investigate the characteristics of functional ligand-receptor pairs and their potential use and applications.

The research team led by Gordon Keller of the McEwen Centre for Regenerative Medicine in Toronto, Canada, created the heart cells from human embryonic stem cells. Researchers found that treating the embryonic stem cells with growth factors encourage them to develop into cardiovascular progenitor cells which have the potential to become any of three specialized types of heart cell — two muscle cell types (cardiomyocytes and vascular smooth muscle) and endothelial cells.

When these progenitor cells were grown in a dish, they developed their own intrinsic 'heartbeat'. What's more, when researchers transplanted a mixture of the three cell types into the hearts of mice with simulated heart disease, their heart function improved significantly. Although not yet tested in humans, the technique could offer a useful way to patch up heart muscle damaged by a heart attack.

Gene therapy success 'reverses' blindness

Experimental gene therapy trials have improved the vision of four people who suffer from hereditary blindness.

The preliminary results of two independent studies suggest that "repair" genes delivered to the eye might one day cure Leber congenital amaurosis (LCA), a rare disease that strikes about 1 in 80,000 people in the UK, and 2,000 Americans in total.

Equally important, say researchers, the treatments proved safe in the six patients who received the genes – delivered by a disabled virus – via eye surgery.

"This is really an exciting result for gene therapy as a field," says Katherine High, of the University of Pennsylvania Medical School in Philadelphia, who was part of an international team that presented the findings at a conference yesterday.

Another team led by Robin Ali, of University College London, presented similar results.

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New Molecule Could Be Key To Anti-heart Attack Drug

Heart attacks are commonly caused by blood clots formed of blood platelets. A new research suggests that it should be possible to create a clot-busting pill that targets a receptor on the blood cells’ surface, something that high-risk patients could take at the first sign of chest pain.

The key to such a pill is according to the research findings a receptor called αIIbβ3 on the platelets’ surface that is intimately involved in the aggregation process. Interfering with αIIbβ3 can prevent an unwanted thrombus and the three αIIbβ3 inhibitors currently on the market can do just that. But they also have side effects and risks and must be administered intravenously. Researchers at Rockefeller University have found a new molecule, called RUC-1, that not only appears to sidestep these problems but, unlike existing drugs, could be taken orally.

Nicholas Piramal India Limited to Piramal Healthcare Limited

Nicholas Piramal India Limited ("NPIL", name proposed to be changed to Piramal Healthcare Limited) is one of India's largest pharmaceutical companies, with a growth track record of above 30% CAGR since 1988. NPIL had consolidated revenues of US$602 million in 2006-07. The Company is currently ranked 4th in the Indian market with a diverse product portfolio spanning nine therapeutic areas. The Company is also one of the largest custom manufacturing companies with a global footprint of assets across North America, Europe and Asia. NPIL is listed in India on the National Stock Exchange (Ticker: NICOLASPIR) and the Bombay Stock Exchange (Ticker: 500302). The name change from Nicholas Piramal India Limited to Piramal Healthcare Limited is subject to approval by the Company's shareholders and Central Government.