New peptide strategy may protect brain cells involved in Parkinson's disease

Researchers at the Federal University of São Paulo (UNIFESP) in Brazil 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, which was conducted in mice, were published in the journal Neuropharmacology.

The study, which was supported by FAPESP, evaluated the effect of a peptide (Ac2-26) – a fragment of a protein (Annexin A1) – on the disease. This protein is produced naturally in both rodents and humans, and previous animal studies have shown that the molecule controls neuroinflammation associated with Parkinson's disease and reduces neuronal degeneration.

Parkinson's disease is closely linked to neurons that synthesize and release dopamine, an essential neurotransmitter for motor functions, motivation, reward, and pleasure. As these neurons degenerate and die due to the disease, the body loses the ability to synthesize dopamine. Without this substance, patients experience impairments such as freezing of gait (difficulty walking) and tremors.

"It's still an experimental study in its very early stages, but it offers an interesting approach by presenting a different strategy from conventional treatment. The peptide acts on neuroinflammation rather than on dopamine replacement. That's important because, in neurodegenerative diseases, there's an inflammatory reaction that affects not only neurons, but also surrounding cells, and the peptide mitigates that process, consequently protecting the brain from cell death," says Cristiane Damas Gil, head of the Department of Morphology and Genetics at the São Paulo School of Medicine (EPM) at UNIFESP and author of the study.

There is currently no cure for Parkinson's disease. Treatment primarily focuses on controlling motor symptoms resulting from dopamine deficiency. The therapeutic approach is therefore based on using levodopa, a dopamine precursor that acts specifically on dopaminergic neurons.

"This medication is considered the gold standard, offering significant benefits, especially in the early stages or during acute treatment, when it leads to a marked improvement in motor symptoms. However, long-term use diminishes its effectiveness and can lead to the development of motor complications and fluctuations in the therapeutic response. That's why it's essential to seek treatment alternatives for such a complex disease as Parkinson's," explains Luiz Philipe de Souza Ferreira, a FAPESP scholarship recipient who conducted the research.

The Ac2-26 peptide is a well-known anti-inflammatory agent that has been tested for other diseases, though it has not yet been developed into a medication. Furthermore, studies indicate that Annexin A1 is altered in Parkinson's disease and is associated with brain inflammation and the dopaminergic neurons involved in controlling movement.

Males and females

To simulate Parkinson's disease, the researchers injected a neurotoxic drug into the animals' brains, inducing neuronal death and typical symptoms of the disease. Almost simultaneously with the intracerebral injection, the researchers administered the peptide intraperitoneally (into the abdomen).

The study also showed differences in protection and disease progression between male and female mice. Following the injury that simulated Parkinson's disease, the researchers observed that females performed better on movement tests initially, but this difference disappeared over time. "That greater resilience was present even in the absence of the Annexin A1 protein," says Gil.

Experiments were conducted on animals with the protein and on genetically modified animals without it.

"In males, however, the loss of neurons was more evident, which allowed us to clearly assess the effects of treatment with the Ac2-26 peptide, which is capable of protecting against degeneration," says Ferreira.

The experiments also revealed that inducing the disease profoundly alters the reproductive cycle of females, highlighting how Parkinson's affects the endocrine system. "This reinforces the need for specific protocols for each biological sex," Ferreira emphasizes.

The current study showed that the peptide acts preventively, 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's proven, then the peptide becomes a more promising treatment candidate," Gil concludes.