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 on 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 naturally produced in both rodents and humans, and previous animal studies have shown that the molecule controls the neuroinflammation associated with Parkinson’s disease and reduces the degeneration of neurons.
Parkinson’s disease is closely related 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 is 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 and not on dopamine replacement. This is important because, in neurodegenerative diseases, there is an inflammatory reaction that affects not only the neurons, but also the brain cells that the peptide protects from 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 focuses primarily on controlling motor symptoms resulting from dopamine deficiency. The therapeutic approach is therefore based on the use of levodopa, a dopamine precursor that acts specifically on dopaminergic neurons.
“This drug is considered the gold standard, it offers significant benefits, especially in the initial stages or during acute treatment, when it leads to a noticeable improvement in motor symptoms. However, long-term use reduces its effectiveness and can lead to the development of motor complications and fluctuations in the therapeutic response. Ferreira, FAPESP scholarship who conducted the research.
The Ac2-26 peptide is a well-known anti-inflammatory agent that has been tested for other diseases, although it has not yet been developed into a drug. In addition, studies show that annexin A1 is altered in Parkinson’s disease and is associated with brain inflammation and dopaminergic neurons involved in movement control.
Males and females
To simulate Parkinson’s disease, researchers injected a neurotoxic drug into the animals’ brains, causing 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. After the injury that simulated Parkinson’s disease, the researchers noticed that the women performed better on the movement tests initially, but this difference disappeared over time. “This greater resistance 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 men, however, neuronal loss was more evident, which allowed us to clearly evaluate the effects of treatment with the Ac2-26 peptide, which is able to protect against degeneration,” says Ferreira.
The experiments also revealed that the induction of the disease profoundly changes the reproductive cycle of females, highlighting how Parkinson’s affects the endocrine system. “This reinforces the need for specific protocols for each biological sex,” emphasizes Ferreira.
The current study showed that the peptide acts preventively by interfering with the initiation of damage. “Our next step is to investigate whether the peptide can reverse the damage caused by Parkinson’s disease. If this is proven, then the peptide becomes a more promising treatment candidate,” concludes Gil.
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