One protein causes the failure of another that is involved in memory and learning, showed a research from the Institute of Neurosciences of Alicante, Spain. The team of scientists has also found that a particular gene, already associated as a main risk factor for developing Alzheimer’s, also interferes negatively in the control of this protein.

With an increasingly long life expectancy and an increasingly aging population, the main challenge of current medicine is the development of treatments for neurodegenerative diseases such as Alzheimer’s. Basic research is essential to develop markers and therapies, especially if we consider that the latest drug to treat this disease was approved 14 years ago and only slows down the rate of progression.

The study focuses on the role of a protein called Reelin, which could participate in memory loss and learning difficulties –characteristic of Alzheimer’s disease. The group of Javier Sáez Valero, researcher at the Institute of Neurosciences of Alicante, just found another piece in the complicated puzzle of Alzheimer’s disease, by deciphering part of the mechanism by which Reelin protein fails in its important function related to memory and learning.

In previous studies we showed that Reelin levels are increased in the brains of people with Alzheimer’s disease. Later we saw that, despite this increase, Reelin paradoxically failed in its functions, which are related to memory processes and synaptic plasticity, “explains Sáez Valero.

Synaptic plasticity, which is affected in Alzheimer’s, is a process by which the connections between neurons (synapses) weaken or reinforce depending on the daily experience. Thanks to this plasticity we can memorize, learn and adapt to new situations.

Functions of the protein involved in memory

In this new work, published in  FASEB Journal , researchers from the Institute of Neurosciences of Alicante UMH-CSIC have found that the ineffective increase in Reelin observed in people with Alzheimer’s is due to a failure induced by beta-amyloid protein, characteristic of Alzheimer’s disease.

Under normal conditions, Reelin binds to a neuron receptor called ApoER2 to perform its function and at the same time maintain its production at adequate levels. “In the brain of people with Alzheimer’s disease, although there is more Reelin, it does not interact correctly with the ApoER2 receptor, because of the interference caused by the beta-amyloid protein. This interference causes a loop that allows the overproduction of Reelin that is not functional,” explains Dr. Sáez Valero.

They have also found that the mechanism that controls the Reelin protein works differently in people carrying the ApoE4 allele, a main genetic risk factor for Alzheimer’s disease. ApoE4 appears to interfere additionally in the control of the Reelin protein, which is involved in memory and learning.

The next step in this research will focus on ApoE to decipher whether the propensity to develop this neurodegenerative disease has to do with these failures in the Reelin that they have detected. The team of Sáez Valero considers important to clarify these alterations, since they can affect the Reelin’s ability to protect the brain against the toxicity of the amyloid beta protein, characteristic of the pathology.

 

Source: SINC