A project led by Dr. Alfonso González de la Rosa, principal investigator at Centro Ciencia & Vida and full professor at Universidad San Sebastián, provided new background on how systemic lupus erythematosus (SLE) can affect the brain and alter metabolic functions, while also opening potential avenues for future therapeutic strategies.

Lupus is an autoimmune disease in which the immune system, instead of defending the body only from external agents like viruses or bacteria, begins to attack its own tissues. In some patients, this process can compromise the nervous system and cause memory problems, cognitive difficulties, and even psychiatric symptoms. Among those living with the disease, these manifestations are often described as "lupus fog," a persistent feeling of confusion, forgetfulness, and difficulty concentrating that impacts daily life.

With the goal of better understanding this phenomenon, the team studied a specific type of autoantibodies called anti-P proteins (anti-P), present in some lupus patients. The work focused on how these antibodies interact with a protein called NSPA, located on the surface of neurons in different regions of the brain.

The results showed that these autoantibodies can alter communication between neurons, especially in the hippocampus, a key brain area for memory. Through experimental models, researchers observed that the antibodies reduce the number of receptors fundamental for nerve signal transmission and modify the structure of synapses, the connections that allow information exchange between neurons. This damage translated into impaired spatial memory.

The research also detected other relevant effects: reduced formation of new neurons, loss of some nerve cells, and activation of microglia, a type of brain immune cell involved in inflammatory responses. Taken together, these changes show that the action of autoantibodies can compromise both brain structure and function.

“This study allowed us to advance our understanding of how certain autoantibodies present in lupus can affect functions as complex as memory and also metabolic processes. These findings not only provide new knowledge about the disease but also open opportunities to explore future therapeutic targets that can improve patients' quality of life,” noted Dr. Alfonso González de la Rosa.

One of the most relevant findings was the identification of an enzyme called PTPMEG, whose activity increases in the presence of these antibodies and which could be involved in the loss of neuronal receptors at the synapse. According to the work directed by Dr. González de la Rosa, this enzyme could become a potential therapeutic target, as could microglia, to try to halt or reduce the neurological damage associated with lupus.

 

But the results were not limited to the brain. The team led by the principal investigator of the Centro Basal Ciencia & Vida, of the Fundación Ciencia & Vida - Universidad San Sebastián, also discovered that the NSPA protein would have an important role in the hypothalamus, a brain region that regulates metabolic functions. In experimental models, the absence of this protein was associated with changes in body weight, alterations in glucose metabolism, and greater fat accumulation. This suggests that anti-P antibodies could be related not only to cognitive problems but also to metabolic alterations observed in people with lupus.

The project also explored compounds with therapeutic potential such as curcumin, which showed protective effects against neuronal damage caused by excessive calcium influx induced by these antibodies. Added to this are the results obtained with galectin-8, a protein that also exhibited neuroprotective properties.

In an additional line of research, the study observed that anti-P antibodies can also affect cancer cells, a finding that opens a novel research path regarding their eventual use in cancer therapies or in strategies to modulate their effects according to the biological context.

Taken together, the findings provide a better understanding of how certain autoantibodies can influence neurological and metabolic symptoms of lupus, and provide new clues for considering future treatments aimed at improving patients' quality of life.