Researchers at Unifesp (Federal University of São Paulo) discovered a new strategy that could, in the future, protect neurons and other brain cells involved in Parkinson’s disease.
The results of the study carried out on mice.
In the research, supported by Fapesp, researchers evaluated the effect of , or “a piece” of a protein (Annexin A1) on the disease. The protein is produced naturally in both rodents and humans, and animal tests have shown that the molecule controls neuroinflammation associated with Parkinson’s, as well as reducing neuronal degeneration.
Parkinson’s disease is closely linked to , a neurotransmitter essential for motor functions, motivation, reward and pleasure. With illness and the loss of these neurons, the body loses the ability to synthesize dopamine. Without this substance, patients suffer losses such as freezing of gait (difficulty walking) and tremors.
“It is still an experimental study, very initial, but it brings an interesting proposal as it presents a different strategy to conventional treatment. The peptide acts on neuroinflammation and not on dopamine replacement. This is important, as in neurodegenerative diseases there is an inflammatory reaction that affects not only neurons, but other surrounding cells, and the peptide acts to mitigate this process and, consequently, protect the brain from cell death”, says Cristiane Damas Gil, head of the Department of Morphology and Genetics at the School Paulista de Medicina (EPM) from Unifesp and author of the work.
Currently, Parkinson’s disease has no cure, being for the control of motor symptoms, resulting from dopamine deficiency. The therapeutic resource is therefore based on the use of levodopa, a precursor of dopamine, with action directed at dopaminergic neurons.
“This medication is considered the gold standard, presenting significant benefits, especially in the initial phases or in acute use, when it promotes significant improvement in motor symptoms. However, with chronic use, its effectiveness tends to decrease, in addition to being able to lead to the development of motor complications and fluctuations in the therapeutic response. Therefore, it is essential to search for treatment alternatives for a disease as complex as Parkinson’s”, explains Luiz Philipe de Souza Ferreira, a Fapesp fellow who carried out the investigation.
The Ac2-26 peptide is a known anti-inflammatory and has already been tested for other diseases, although it has not yet become a medicine. Furthermore, studies indicate that Annexin A1 is altered in Parkinson’s disease, being associated with both brain inflammation and dopaminergic neurons involved in movement control.
Males and females
To simulate Parkinson’s, the researchers injected a neurotoxic drug into the animals’ brains, thus inducing neuronal death and typical symptoms of the disease. Almost simultaneously with the intracerebral injection, the researchers applied the peptide intraperitoneally (in the abdomen).
The study also showed that there are differences in protection and disease progression between male and female mice. The researchers observed that after the Parkinson’s-mimicking lesion, females performed better on movement tests at the beginning of the experiment, but this difference disappeared over time. “This greater resistance was present even in the absence of the Annexin A-1 protein”, says Gil.
In the study, experiments were carried out both on animals that had the protein and on those that were genetically modified to be without it.
“In males, the loss of neurons was more evident, which allowed us to clearly evaluate the effects of treatment with the Ac2-26 peptide, capable of protecting the condition from degeneration,” says Ferreira.
The experiments also revealed that the induction of 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”, he highlights.
The current study showed that the peptide works preventatively, acting simultaneously with the onset of damage. “Our next step is to investigate whether the peptide works by reversing the damage caused by Parkinson’s disease. If this is proven, it will elevate the peptide to a more interesting treatment candidate”, concludes Gil.
