Scientists are proving the therapeutic potential of a new chemical compound against Alzheimer’s disease

A scientific team led by the neuropharmacologist Maria José Diógenes confirmed in experiments with mice the therapeutic potential of a new chemical compound against Alzheimer’s disease, the most common form of dementia that affects memory and language.

“This compound is completely innovative, because it has a completely different mechanism of action than other compounds and medicines that have been studied for Alzheimer’s disease”, said the researcher at the Institute of Pharmacology and Neurosciences at the University Faculty of Medicine Lisbon to Lusa.

Tested on mice that resemble Alzheimer’s disease, the amino acid compound created by the research group in the laboratory and called TAT-TrkB “prevented memory loss and learning without showing anti- effects. “

“At the molecular level, it was possible to see the absence of changes that are usually found in the brains of patients with Alzheimer’s disease”, said Maria José Diógenes, on the eve of the World Day for People with Alzheimer’s Disease, celebrated every year in September 21st.

The work, described in an article recently published in the journal Molecular Therapy and signed by an international team of scientists, was celebrated in 2021 by the Misericórdia de Lisboa with one of the Santa Casa Neuroscience Awards.

At the time, speaking to Lusa, the researcher and professor Maria José Diógenes said that she proposed to “prove the therapeutic potential of a compound” created by a large research team in a previous study.

The compound was designed “to protect the neuroprotective effects of a very important molecule for the brain, BDNF”, which is “crucial for memory and learning processes” and whose function is “reduced” in Alzheimer’s patients due to “the site where the molecule binds. to bring about its effect it is destroyed.”

“Over many decades, researchers from around the world have dedicated themselves to studying ways to increase BDNF, however, they have not dedicated themselves to study of the lock, the receptor”, said the neuropharmacologist now to Lusa, clarifying that the new compound, TAT. – TrkB, “prevents the cleavage” of the receptor of the molecule, called ‘ TrkB-FL’.

“For BDNF to produce its effects, it has to activate the TrkB-FL receptor, it’s like BDNF is the key and the receptor is the lock. For the key to open the door, the lock must be intact”, he explained.

In Alzheimer’s disease, the lock, the ‘TRKB-FL’ receptor, is broken and “breakage of the receptor creates two fragments”, and “one of them has the ability to stimulate memory change and change the activity of genes”. The researcher explained that his team previously analyzed samples “collected from the brain autopsies of Alzheimer’s patients” and performed studies on neurons (cells of the nervous system) and animal models.

Following this work, the team tested the efficacy and toxicity of the compound in cell cultures, brain slices and synaptic terminals from dead animals and in living rodents that mimicked Alzheimer’s disease (versus animals healthy). To understand the differences, scientists gave a placebo to “sick” mice and healthy mice.

The team of Maria José Diógenes found that when given to rodents that had regenerated Alzheimer’s disease, the new chemical compound “recovers the functions of the BDNF molecule in the brain,” by preventing the breakdown the TrkB-FL receptor”, and “prevents the formation of a toxic fragment that can spread the disease”.

In addition, the new substance “reduces levels of hyperphosphorylated Tau, a peptide [composto de aminoácidos] which accumulates in the brains of Alzheimer’s patients and is believed to be one of the causes of the disease”, and “prevents the loss of dendritic spines, structures that allow neurons to communicate with each other and which is necessary for the formation of memory”.

Actions that, according to the researcher, “lead to the improvement of memory and learning of Alzheimer’s disease model mice in a very strong way without the appearance of side effects.” “

Until the new compound can be tested on humans, Maria José Diógenes and the rest of the team will “work to develop routes and methods of administration” of the substance. “We are also investigating other compounds with a different chemical structure to maximize the likelihood of compounds with this mode of action going to clinical trials,” he told Lusa.