The main objective of the research team run by Dr. Alejandra Alvarez and Dr. Silvana Zanlungo, part of the School of Biological Sciences and the School of Medicine at the Pontifical Catholic University of Chile, is to find new molecules that are inhibitors of the protein responsible for producing neuronal death and Alzheimer’s disease. It is important to note that currently no treatment or cure for this disease exists in the world.

“We have found that by inhibiting a specific protein kinase, it is possible to slow the progression of the disease in transgenic animal models of Alzheimer’s disease. As they age these animals show a progressive loss of memory and cognitive abilities, associated with a series of markers in the brain, similar to those found in patients with this syndrome,” explains Dr. Alvarez.

Studies at the Center for Aging and Regeneration (CARE Chile UC) have shown that therapy performed with inhibitory molecules of this protein decreases neuronal death and the deposit of the toxic peptide in the disease, thus delaying cognitive decline and the onset of Alzheimer’s.

Alejandra-Álvarez_LaboratorioThe mechanisms through which neuronal death and cognitive impairment occur in this disease are only partially known. This research is significant in that it would help clarify this scenario for the international scientific community. “This is a very important scientific and medical discovery because finding the neurotoxic peptide receptor for Alzheimer’s disease would allow us to try to block it and develop therapeutic strategies for it in the future,” says the specialist.

Protein in cancer

Dr. Alexandra Avarez explains that this protein is described in the cancer process and that it helps the proliferation of malignant cells. However, in the context neurons is an inducer of cell death. “When its signal is activated, it begins an early start of the elimination of synapses, followed by the death of the neuron. Then a kinase integrates the downstream mechanisms that lead to a loss of memory and cognitive abilities.”

This is explained by the fact that the kinase is mutated in cancer, in other words, it is fused with another abnormal protein that promotes the proliferation of diseased cells. However, in a normal cell, the kinase would not be mutated and its activation would induce cell death, cytoskeleton modification, and decreased functionality of the neuron.

The research, “Identification of inhibitors of the c-Abl kinase for the potential treatment of Alzheimer’s disease,” received funding from the XVIII National Research and Development (R & D) Fondef Project Competition, 2012. This allowed them to advance the analyses to currently be in the pre-clinical stage, waiting to get new resources to further advance the development of this therapy.

Signaling pathways

In addition to Alzheimer’s disease, the research conducted by the team of specialists at CARE UC, seeks to understand the pathways or signaling mechanisms involved in neuron cell death associated with other neurodegenerative diseases such as Parkinson’s and Amyotrophic Lateral Sclerosis (ALS) .

“Our main neurodegenerative disease target is Alzheimer’s, but we are also studying in partnership with other laboratories the Niemann-Pick disease, a disease that mainly affects children and who have a life expectancy of no more than 18 years of age,” says the researcher.

Alzheimer’s in Chile

Alzheimer’s disease is one of the most frequent causes of death according to statistics from the World Health Organization (WHO). It usually affects people over 65 years of age and causes irreparable brain damage. “This disease causes a gradual and steady deterioration of intellectual abilities. In the brain neurons are dying as a result of the amyloid beta peptide accumulation, which turns out to be toxic and produces neuronal dysfunction,” emphasizes Dr. Alvarez

According to data provided by the Alzheimer’s Corporation of Chile, in our country, the elderly make up more than 10% of the population. Many of them may have cognitive disorders, so an early diagnosis can significantly improve people’s quality of life of people.

One in eight senior citizens may have the disease and after 85 years of age, the probability is 1 in 2, figures that are alarming, considering that Chile has one of the oldest populations on the continent.

“Advances in the understanding of Alzheimer’s disease, allow us to slow cognitive decline and thereby improve the quality of life of the patients. We are confident that we can continue achieving excellent results in our research, and we hope that in the near future Chile can develop a new therapy to combat Alzheimer’s,” concludes Dr. Alejandra Alvarez. (By Maria Mercedes C. Barraza Agency. Inés Llambías Communications).