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A protein ‘passport’ that helps nanoparticles get past immune system

A protein ‘passport’ that helps nanoparticles get past immune system | Longevity science | Scoop.it

Macrophages — literally, "big eaters" — are a main part of the body's innate immune system . These cells find and engulf invaders, like bacteria, viruses, splinters and dirt. Unfortunately, macrophages also eat helpful foreigners, including nanoparticles that deliver drugs or help image tumors.


Along with members of his lab, Dennis Discher, professor of chemical and biomolecular engineering in the School of Engineering and Applied Science, has developed a "passport" that could be attached to therapeutic particles and devices, tricking macrophages into leaving them alone. 

Taking a cue from a membrane protein that the body's own cells use to tell macrophages not to eat them, the researchers engineered a the simplest functional version of that protein and attached it to plastic nanoparticles. These passport-carrying nanoparticles remained in circulation significantly longer than ones without the peptide, when tested in a mouse model.


In 2008, Discher’s group showed that the human protein CD47, found on almost all mammalian cell membranes, binds to a macrophage receptor known as SIRPa in humans. Like a patrolling border guard inspecting a passport, if a macrophage’s SIRPa binds to a cell’s CD47, it tells the macrophage that the cell isn’t an invader and should be allowed to proceed on.

 

“There may be other molecules that help quell the macrophage response,” Discher said. “But human CD47 is clearly one that says, ‘Don’t eat me’.” Since the publication of that study, other researchers determined the combined structure of CD47 and SIRPa together. Using this information, Discher’s group was able to computationally design the smallest sequence of amino acids that would act like CD47. This “minimal peptide” would have to fold and fit well enough into the receptor of SIRPa to serve as a valid passport. After chemically synthesizing this minimal peptide, Discher’s team attached it to conventional nanoparticles that could be used in a variety of experiments. “Now, anyone can make the peptide and put it on whatever they want,” Rodriguez said.

 

The research team’s experiments used a mouse model to demonstrate better imaging of tumors and as well as improved efficacy of an anti-cancer drug-delivery particle.

 

As this minimal peptide might one day be attached to a wide range of drug-delivery vehicles, the researchers also attached antibodies of the type that could be used in targeting cancer cells or other kinds of diseased tissue. Beyond a proof of concept for therapeutics, these antibodies also served to attract the macrophages’ attention and ensure the minimal peptide’s passport was being checked and approved.


Video is here: http://tinyurl.com/b6dthgb


Via Dr. Stefan Gruenwald
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Parkinson’s breakthrough could slow disease progression | KurzweilAI

Parkinson’s breakthrough could slow disease progression | KurzweilAI | Longevity science | Scoop.it

Northwestern University scientists have developed a new family of compounds that could slow the progression of Parkinson’s disease.

 

Parkinson’s, the second most common neurodegenerative disease, is caused by the death of dopamine neurons, resulting in tremors, rigidity and difficulty moving. Current treatments target the symptoms but do not slow the progression of the disease.

 

The compounds work by blocking calcium. The compounds target and shut a relatively rare membrane protein that allows calcium to flood into dopamine neurons.

 

 

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Potential for blood test to detect lung cancer in early stages

Potential for blood test to detect lung cancer in early stages | Longevity science | Scoop.it

While the overall lung cancer five-year survival rate in the U.S. is 15 percent, the odds of survival increase significantly with early detection. However, the expense or invasiveness of current screening methods and the lack of symptoms at early stages of the disease means most people aren’t diagnosed until the cancer is well advanced.

 

Findings by researchers at the University of York could pave the way for a simple blood test that would detect the disease even in its early stages.

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Chemical that slows down the biological clock could lead to new drugs to treat diabetes

Chemical that slows down the biological clock could lead to new drugs to treat diabetes | Longevity science | Scoop.it

Scientists have long suspected that metabolic disorders, such as type 2 diabetes and obesity, could be linked to our circadian rhythm or biological clock. For example, laboratory mice with altered biological clocks often become obese and develop diabetes.

 

Now biologists at UC San Diego have discovered that a chemical, which affects the activity of a key protein that regulates our biological clock, can repress the production of glucose by the liver, offering a promising new direction for the development of a new class of drugs to treat diabetes.

 

A team headed by Steve Kay, dean of the Division of Biological Sciences at UC San Diego, had previously found that altering the levels of a key protein, called cryptochrome – which regulates the biological clocks of plants, insects and mammals and also regulates glucose production in the liver – could improve the health of diabetic mice.

 

Building on that research...

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Revved-Up Protein Fights Aging - ScienceNOW

Revved-Up Protein Fights Aging - ScienceNOW | Longevity science | Scoop.it
An unlikely, decadelong journey that began with the discovery of a rapidly aging mouse has led scientists to a protein that seems to protect animals from cancer and other scourges of old age—with no apparent downsides. There are still lots of mysteries about the protein, called BubR1, but the work offers clues about how protecting chromosomes can enhance health.
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New Biomarker May Allow Earlier Diagnosis of Mesothelioma

"Researchers have shown that the protein fibulin-3 may be able to distinguish patients with mesothelioma from people with similar conditions and from healthy individuals. Although preliminary, the results suggest that this protein may be a promising new biomarker for diagnosing the disease and possibly informing prognosis. The study was published October 11 in the New England Journal of Medicine.

 

Pleural mesothelioma, a disease of the tissue that lines the chest cavity and covers the lungs (the pleura), is an aggressive cancer often associated with asbestos exposure. Patients diagnosed with this disease have a median survival of 1 year.

 

Diagnosing mesothelioma early, when treatment may be most effective, is difficult because of its long latency period and the lack of reliable methods to detect the disease in its early stages. A protein called soluble mesothelin-related protein is the best-studied biomarker for mesothelioma, but the test for it has low sensitivity, meaning that it fails to detect mesothelioma in some people who have the disease.."


Via Brian Shields
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Protein that boosts longevity may protect against diabetes

Protein that boosts longevity may protect against diabetes | Longevity science | Scoop.it

SIRT1, a protein that slows aging in mice and other animals, also protects against the ravages of a high-fat diet, including diabetes, according to a new MIT study.

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Steve Kingsley's curator insight, October 12, 2013 7:24 PM

Somehow I thought high carb - especially refined sugar - diet was the main culprit in developing diabetes.