Researchers at Brazil’s Federal University of São Paulo (UNIFESP) have discovered a new strategy that may protect neurons and other brain cells involved in Parkinson’s disease in the future. The results of the study conducted on mice were published in a journal. neuropharmacology.
The study, supported by FAPESP, evaluated the impact of a peptide (Ac2-26), a fragment of a protein (annexin A1), on disease. This protein is naturally produced in both rodents and humans, and previous animal studies have shown that this molecule controls neuroinflammation and reduces neurodegeneration associated with Parkinson’s disease.
Parkinson’s disease is closely linked to neurons that synthesize and release dopamine, a neurotransmitter essential for motor function, motivation, reward, and pleasure. When these neurons degenerate and die due to disease, the body loses its ability to synthesize dopamine. Without this substance, patients experience problems such as freezing of foot (difficulty walking) and tremors.
“Although this is an experimental study that is still at a very early stage, it offers an interesting approach by presenting a different strategy to conventional treatments. The peptides act on neuroinflammation rather than dopamine replacement. This is important because in neurodegenerative diseases there is an inflammatory response that affects not only neurons but also surrounding cells, and peptides alleviate that process and thus protect the brain from cell death,” says Christian Damas. Gil, head of the morphogenetics department at UNIFESP’s Medical University of São Paulo (EPM) and author of the study.
There is currently no cure for Parkinson’s disease. Treatment primarily focuses on controlling motor symptoms caused by dopamine deficiency. Therefore, the therapeutic approach is based on the use of levodopa, a dopamine precursor that acts specifically on dopaminergic neurons.
“This drug is considered the gold standard and has a great effect, especially in the early stages and during acute treatment leading to a marked improvement in motor symptoms. However, long-term use can reduce its effectiveness and lead to the development of motor complications and fluctuations in treatment response. Therefore, it is important to look for alternative treatments for complex diseases like Parkinson’s disease,” explains Luis Philippe de Souza Ferreira, a FAPESP scholarship recipient who carried out the study.
The Ac2-26 peptide is a well-known anti-inflammatory agent and has been tested for other diseases, but it has not yet been developed as a drug. Additionally, studies have shown that annexin A1 is altered in Parkinson’s disease and is associated with brain inflammation and dopaminergic neurons involved in controlling movement.
male and female
To simulate Parkinson’s disease, researchers injected neurotoxic drugs into the animals’ brains, inducing nerve cell death and typical symptoms of the disease. At about the same time as the intracerebral injection, the researchers administered the peptide intraperitoneally (in the abdomen).
The study also showed differences in defense and disease progression between male and female mice. After a lesion that mimicked Parkinson’s disease, the researchers observed that women initially performed better on movement tests, but that this difference disappeared over time. “That great resilience was present even in the absence of the annexin A1 protein,” Gill says.
Experiments were carried out on animals that had the protein and genetically modified animals that did not.
“However, neuronal loss was more evident in men, so we were able to clearly assess the effect of treatment with the Ac2-26 peptide, which can prevent degeneration,” Ferreira says.
The experiment also revealed that inducing the disease significantly alters a woman’s reproductive cycle, highlighting how Parkinson’s disease affects the endocrine system. “This reinforces the need for specific protocols for each biological sex,” Ferreira emphasizes.
The current study shows that this peptide acts prophylactically, intervening at the onset of damage. “Our next step is to investigate whether the peptide can reverse the damage caused by Parkinson’s disease. If that is proven, the peptide becomes a more promising therapeutic candidate,” Gill concluded.
sauce:
São Paulo Research Foundation (FAPESP)
Reference magazines:
DOI: 10.1016/j.neuropharm.2026.110942
