University of São Paulo: Discovery involving proteins reinforces the need to do biomedical research with both sexes

ANDa study carried out at USP’s Institute of Biomedical Sciences (ICB) with male and female mice revealed differences as each sex expresses two proteins important to the central nervous system, responsible for the control of several cellular functions: PTEN and Klotho. The discovery, published in an article in the journal Scientific Reports, shows that the variation of protein levels according to sex can be related to the development of diseases and even to the response to treatments. For professor Elisa Mitiko Kawamoto, who conducted the study, the discovery highlights the importance of doing research with both sexes and not focusing only on male animals, as occurs in most works. This would help to think about personalized treatments, suitable for each individual.

The research was part of the master’s dissertation of researcher Natália Prudente de Mello, from the Molecular and Functional Neurobiology Laboratory of the Pharmacology Department at ICB.

According to the researchers, sex can be considered a predictive factor for a number of neurological diseases – autism, for example, is four times more common in boys than girls, according to data from the US Center for Disease Control and Prevention.

The team seeks new treatments for diseases, with an emphasis on neurological diseases – in this case, the proteins PTEN and Klotho were studied as pharmacological targets. When analyzing the expression of these two proteins in healthy mice of both sexes, the scientists found that PTEN was increased in females, while Klotho was more expressed in males. “This indicates that these two signals act in order to maintain the balance of the organism,” says Kawamoto.

PTEN is a tumor suppressor protein and, in the central nervous system, it also interferes in processes of cell proliferation and differentiation, which can be important for learning and memory. In this sense, it is possible that the higher incidence of autism in boys is related to a lower signaling of PTEN, for example. “This protein also plays a major role in inflammation, which is a characteristic of neurodegenerative diseases like Alzheimer’s and Parkinson’s,” he explains. In addition, the neurons of animals with PTEN deletion, studied in the laboratory, proliferate and grow more than normal, causing tumors.


PTEN protein plays a major role in inflammation, characteristic of diseases such as Parkinson’s and Alzheimer’s – Credit: Pixabay
Klotho is the anti-aging protein. There is a reduction in the levels of this protein during aging, especially in the presence of neurodegenerative diseases. “Animals that do not have this gene have an accelerated aging, living at most three months, in addition to having a marked cognitive and motor deficit”, says the researcher. Literature data show that Klotho replacement in these cases improves cognition, locomotor activity and has anti-inflammatory effects.

Individualized treatments
“Just as there is pharmacogenomics, which provides for the development of drugs according to the patient’s genome, there should also be a concern to develop drugs dependent on sex, since men and women have different susceptibilities to certain diseases”, highlights the professor Elisa Mitiko Kawamoto.

In the next steps of the study, scientists will seek to understand why the expression of PTEN and Klotho proteins varies between sexes and whether the hormones testosterone or estrogen may be related to this difference.

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