A study coordinated by the UAB, based on computer models and human cell cultures, shows that big dynorphin, an endogenous opioid peptide, protects neurons against the cytotoxic effects of β-amyloid accumulation.
One of the main features of Alzheimer’s disease is that the β-amyloid peptide, a molecule found inside neurons that has many diverse functions, begins to fold incorrectly and accumulates. This process, which ends up causing neuron death, is linked to a series of other cellular alterations, which are often difficult to determine if whether they are the cause or the consequence. An example is the case of the deregulation of a type of dynorphin.
Dynorphins are the body’s own opioid peptides, which play a key role in many brain pathways. They are located in different areas of the brain, such as the hippocampus, amygdala or hypothalamus, and are involved in memory processes, emotion control, stress and pain, and other processes. In addition, several studies have shown involvement in epilepsy, stroke, addictions, depression, or schizophrenia.
Now, in a study published in the Computational and Structural Biotechnology Journal, a research group led by Àlex Perálvarez-Marín, a researcher in the Department of Biochemistry and Molecular Biology and the UAB Institut de Neurociències, has studied computer models and cell cultures what interactions may exist between β-amyloid peptide and big dynorphin, to determine its role in β-amyloid accumulation.
“The β-amyloid peptide is negatively charged and, on the other hand, dynorphins are positively charged. Since the positive interacts with the negative, and we knew that both peptides are located in the same place, we thought it could be interesting to study the two molecules together”, explained Dr Perálvarez-Marín.
The results show that, due to the physicochemical features of big dynorphin, its presence hinders the amyloid interaction and the formation of β-amyloid peptide aggregates, apart from adding to promoting a neuroprotective effect. In addition, thanks to computational modelling, researchers could be able to obtain clues about which big dynorphin regions interact with the β-amyloid peptide. “From a basic research perspective, the study opens a therapeutical intervention window against Alzheimer’s disease, where the design of therapeutic peptides could represent an advance to stop amyloid aggregation phenomena”, concluded Dr Perálvarez-Marín.
The study proposes new approaches in the search for treatments for Alzheimer’s disease using therapeutic peptides based on big dynorphin, and proposes suggests exploring the specific advantages of an endogenous neuropeptide, capable of crossing the blood-brain barrier to reach the brain and preventing amyloid aggregation.