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Rapid delivery: Injected protein flips a switch in the brain, disappears

Rapid delivery: Injected protein flips a switch in the brain, disappears

A protein that is modified and injected into the brains of rats can rapidly change how the rodents behave, and the effects last for days or even weeks. The finding suggests that it may be possible to use similar techniques to change the activity of specific brain circuits in people with neuropsychiatric disorders.

The researchers found that the protein, called ephrin-A1, flips a switch in the brain that controls activity in a circuit that includes the prefrontal cortex and the striatum. This circuit is thought to be important for attention, flexible thinking and other higher-order cognitive functions.

When the rats were injected with ephrin-A1, they became more active and exploratory, and they spent more time in an area of their cage that was novel to them. The effects lasted for at least 10 days.

The protein also increased the activity of neurons in the prefrontal cortex and striatum, and it increased the number of connections between those regions.

The findings suggest that it may be possible to use proteins to transiently and reversibly change the activity of specific brain circuits. Such a approach could potentially be used to treat neuropsychiatric disorders.

A team of researchers from Harvard University and Massachusetts General Hospital have developed a new way to deliver therapeutic proteins into the brain, using a specially designed “smart” protein that can cross the blood-brain barrier and target specific cells.

The new approach, described in a paper published in the journal Nature Biomedical Engineering, could potentially be used to treat a variety of neurological diseases, including Alzheimer’s, Parkinson’s, and ALS.

The blood-brain barrier (BBB) is a natural barrier that protects the brain from harmful substances in the blood. However, it also prevents many therapeutic drugs from reaching the brain, making it a major challenge for treating neurological diseases.

To overcome this obstacle, the researchers designed a new type of protein that can bind to a specific target on the surface of brain cells and cross the BBB. The protein, which the researchers call “TAT-CL4D2,” is a fusion of two proteins: the “TAT” protein, which is derived from the HIV virus and can cross the BBB, and a “CL4D2” protein, which binds to a specific receptor on the surface of neurons.

When TAT-CL4D2 is injected into the bloodstream, it bindsto the receptors on neurons and crosses the BBB. Once in the brain, it is taken up by the target cells and delivered to the neuron’s nucleus, where it can “flip a switch” to turn on genes that are involved in the disease.

Importantly, TAT-CL4D2 is “smart” enough to only bind to and cross the BBB when it is injected into the bloodstream. This is crucial because it prevents the protein from accidentally binding to and crossing the BBB when it is not injected, which could lead to harmful side effects.

In a proof-of-concept study in mice, the researchers showed that TAT-CL4D2 can deliver a therapeutic protein to the brain and reverse the symptoms of Alzheimer’s disease.

The study found that TAT-CL4D2-delivered proteins were able to cross the BBB and reach the target cells in the brain. The proteins were then taken up by the cells and delivered to the nucleus, where they turned on genes that are involved in the disease.

Furthermore, the study showed that TAT-CL4D2-delivered proteins were able to reverse the symptoms of Alzheimer’s disease in mice.

This new approach has the potential to revolutionize the way we treat neurological diseases, and the researchers are already working on translating it to the clinic.

The current study was funded by the National Institutes of Health, the Alzheimer’s Association, and the Michael J. Fox Foundation for Parkinson’s Research.

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