Alzheimer's Disease and the Wnt signaling pathway
The decline in the activity of the Wnt pathway is related to the development of Alzheimer's disease
sci-lib based on ScienceDaily: Pathway that contributes to Alzheimer's disease revealed by researchResearchers at the Mayo Clinic in Jacksonville have identified a defect in one of the most important signaling pathways in the cell.
According to them, this defect leads both to the hyperproduction of toxic protein in the brain of people who have Alzheimer's disease, and to a violation of the interaction between neurons. Both the first and second events significantly contribute to the development of Alzheimer's disease.
The results of the study indicate that the detected defect can be eliminated with the help of special drugs, normalizing the flow of the damaged signaling pathway.
"The defect in question is not the only cause of the development of Alzheimer's disease. As the data we have obtained show, it is very important and can be eliminated therapeutically. Thus, it is probably possible to resist the development of Alzheimer's or treat the disease in the early stages of development," says Guojun Bu, neurologist at the Mayo Clinic.
We are talking about the Wnt path. It plays a fundamentally important role in cell survival, embryonic development and synaptic activity (transmission of signals that are necessary for normal memory and learning). Any deviations in the course of the Wnt pathway (too high / low activity) lead to illness. For example, in the case of its excessive activation, the cells of the body begin to grow uncontrollably (the risk of developing cancer increases significantly).
Although many studies on Wnt have focused on diseases that develop with hyperactivation of this pathway, a group of scientists led by Dr. Bu has shown a link between Alzheimer's disease and suppressed Wnt activity.
"Our discovery is quite logical, since many researchers have long known that patients who are diagnosed with cancer are at a lower risk of developing Alzheimer's disease, and vice versa," says Dr. Bu. According to him, it remained unknown whether the Wnt path was involved in this. Using experimental mice, scientists have identified a key defect that leads to suppression of Wnt against the background of Alzheimer's disease. They found a deficiency of the protein "LRP6" (LRP6 – low-density lipoprotein receptor-related protein 6). Experts have found that LRP6 regulates both the production of amyloid beta, a protein that is deposited in the brain of people suffering from Alzheimer's disease, and communication between neurons. The activity of LRP6 below the normal level leads to the accumulation of beta-amyloid protein and disrupts the ability of neurons to communicate.
Loss of LRP6 in neurons (right) leads to increased deposition of amyloid protein– a marker of Alzheimer's disease.
In mice, in whose body the production of LP6 is suppressed, a violation of the Wnt pathway, cognitive functions, as well as an excess of amyloid protein is detected. The authors of the study verified the discovery by using brain tissue from deceased patients with Alzheimer's disease. They found a deficiency of the LRP6 protein and a significant decrease in the activity of the Wnt pathway.
The creation of compounds capable of normalizing the activity of the LP6 and Wnt pathways can help increase the effectiveness of the fight against Alzheimer's disease.
A more detailed description of the results of the study can be found on the web pages of the journal Neuron (Liu et al., Deficiency in LRP6-Mediated Wnt Signaling Contributions to Synaptic Abnormalities and Amyloid Pathology in Alzheimer's Disease - VM).
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