This contribution is a preliminary step in studying proteins in patient samples to prevent their accumulation and thus related symptoms. The experimental data were obtained from a mouse animal model created by the researchers, which reproduces the accumulation of protein fragments during the disease.
In the published work, researchers focused on the fragment of synaptic protein neurexin, which is called nrxnctf in the scientific community. This fragment accumulates in the case of a mutation in the presenilin gene that causes familial Alzheimer's disease. The researchers observed that their experimental accumulation in the brain of animal models can lead to specific memory defects. Experimental models of these diseases are very important for determining the pathogenesis and designing the basis of effective therapy.
The researchers observed in behavioral studies that the accumulation of this protein leads to the loss of associative memory dependent on the brain's amygdala. In collaboration with Jos é Mar í a Delgado of the University of Pablo de oravide, synaptic connections from the prefrontal cortex to the amygdala were studied using electrophysiological records in mice. These experiments show that the accumulation of nrxnctf can also produce presynaptic plasticity defects.
Neurexin
Neurexin is a transmembrane protein expressed in neurons and (neuroendocrine) cells. Neurexin exists in a variety of subtypes because they are encrypted by three genes, which are transcribed by two promoters and further modified by extensive alternative splicing. α－ Neurexin and β－ Neurexin protein consists of ligand binding domains that bind to several extracellular and intracellular interaction partners. Mouse genetics has proved α－ Neurexins play an important role in Ca2 + - dependent synaptic transmission and a secondary role in synaptic formation. conversely, β－ Neurexins showed a strong potential to induce and differentiate synapses in cell culture experiments. Therefore, neurexin has become a key synaptic cell adhesion molecule and plays an important role in Ca2 + - triggered release and synaptic development.
