Today's Science: 30 years of mystery solved! Scientists have finally figured out the role of key proteins in Alzheimer's disease

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Today's Science: 30 years of mystery solved! Scientists have finally figured out the role of key proteins in Alzheimer's disease

2019-01-13 09:03:36 172 ℃
< p > In the brains of patients with Alzheimer's disease, there are many deposits of beta-amyloid protein. Is it the cause or effect of Alzheimer's disease? At present, there are still many debates in the academic circles. But there is no doubt that this protein plays an important role in Alzheimer's disease.

There are still many mysteries in the brain waiting for us to solve (Pixabay)

So where did this protein come from? More than 30 years ago, scientists found the source - on chromosome 21, there is a mysterious gene that encodes amyloid precursor protein (APP). This long protein is cut into several segments in the body, one of which eventually leads to beta-amyloid deposition.

says that the gene is mysterious because of our ignorance of it. It has been more than 30 years since < strong > gene was found in < EM > APP . However, the specific function of APP protein remains unknown. Scientists can't help wondering what kind of physiological function this key protein associated with Alzheimer's disease has. The mystery of

has finally been solved today. Scientists from the VIB Institute in Belgium have found that there are specific receptors for APP in the brain. The combination of the two has potential benefits for synapses. This important discovery is also published today in the top academic journal Science. Science magazine also made special reports on it, and reported that the study "may open a new world for Alzheimer's disease". <


This study was published in Science magazine, and received a special report strong> (photo source: < strong >< strong >< strong >< strong >>> < strong > (photo source: (Science)<<<< p>< strong The results of this study are as follows:1. It can't be blamed for scientists'lack of effort. It can only be blamed for the complexity of APP: the protein is cut into many different segments, each of which has different functions. Sometimes, different fragments have opposite effects, which makes it difficult to interpret the experimental results. In addition, several proteins are very similar to APP, which makes it difficult to distinguish them.

But scientists have caught a lot of clues about APP protein, for example, we know that it may perform some extracellular physiological functions. "We know that amyloid precursor proteins release themselves out of the cell to perform certain functions," said Dr Heather Rice, the lead author of the study. "To understand its function, we need to look for proteins that bind to it on the cell surface."

_The first author of this study, Dr Heather Rice (Image Source: VIB Institute)

Researchers focused on adult hippocampus, which is an important area related to memory. Studies have shown that the anterior synaptic end of hippocampal neurons secretes a class of APPs (APPs alpha). They bind to a neuroreceptor called GABABR1a, which inhibits synaptic function. Follow-up studies showed that the binding was specific. Some proteins with similar structure to APP could not bind to GABABR1a smoothly. After further study, scientists found that the binding of < strong > APP depends on a polypeptide fragment consisting of 17 amino acids. The synthetic polypeptide fragment is sufficient to bind to GABABR1a and inhibit the activity of neurons.

_The illustration of this study (Image Source: Science)

So far, the discoveries made by scientists have clarified the role of APP and solved an unsolved mystery for more than 30 years. But what does this have to do with Alzheimer's disease? Why does the special report of science specifically mention "may open a new world for Alzheimer's disease"? It turns out that GABABR1a is very important for maintaining stable synaptic plasticity. Previous studies have shown that in patients with Alzheimer's disease, the levels of APP proteins secreted outside the cell may be disturbed, which may destroy the homeostasis of the neural network. In addition, the lower the protein level of these APPs, the worse the memory performance of the patients. This often happens before the onset of symptoms of Alzheimer's disease. The 17-amino-acid polypeptide mentioned above can bind to GABABR1a. In theory, it is expected to restore the stability of the nervous system and play a protective role.

As reported in Science, "This may lead to new ways of protecting synaptic function and even remodeling synaptic function in patients with Alzheimer's disease!"


<1]Rice et al., (2019), Secreted amyloid-beta precursor protein function s a s a GABABR1a ligand to modulate synaptic transmission, Science, DOI: 10.1126/science.aao4827

<2]Martin Korte, (2019), Neuronal function of Alzheimer's protein, DOI: 10.1126/science.0636

answer-archers Question about protein found in Alzheimer's brain plaques, Retrieved January 10, 2019, from

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