Protein inactivation halts Parkinson's disease progression and improves motor function in an animal model

Researchers from the Cima University of Navarra and the School of Medicine of the University of Navarra have demonstrated that inhibition of a protein, whose expression increases with age and Parkinson's disease, halts disease progression and improves motor function in a humanized model of this pathology.

Parkinson's disease is the second most common neurodegenerative disorder in humans. It affects motor and non-motor functions and its symptoms can manifest in different organs, including cognitive alterations and gastrointestinal problems. Its main characteristic is the progressive loss of dopaminergic neurons, which contain a pigment called neuromelanin.

Despite advances in the development of therapies that control symptoms, there are no strategies to prevent or slow the progression of the disease. "Therefore, it is essential to promote programs of study aimed at identifying new neuroprotective treatments for these patients," explain Drs. Ana García-Osta and Mar Cuadrado-Tejedor, researchers of the group of Gene Therapy for Neurodegenerative Diseases of the Cima.

The scientific team has developed a mouse model that replicates the molecular mechanisms present in the brains of Parkinson's disease patients, such as the accumulation of neuromelanin. "Our findings indicate that the aging process increases the susceptibility of dopaminergic neurons to the accumulation of this pigment, which increases the risk of disease," says the first author of the work, Marta García-Gómara. The results have been published in the scientific journal Molecular Therapy.

New therapeutic strategies

In this experimental model , the researchers have identified a protein, FKBP51, whose presence increases markedly with aging and in brains affected by Parkinson's disease. This finding points to it as a new therapeutic target. "FKBP51 is involved in protein folding, and its overexpression has been associated with neuroinflammatory processes. In our study, we observed that its inhibition protects dopaminergic neurons, reduces neuroinflammation, improves motor function and slows the progression of Parkinson's disease. Therefore, it opens the door to new treatment alternatives," explain the authors of the study.

Following these promising results, the Cima team is now working on the design of specific molecules capable of inhibiting or reducing FKBP5 levels, with the goal of reaching the brain in effective therapeutic concentrations.

The results of this study, carried out within the framework the Institute of Health research of Navarra (IdiSNA), have been funded by the European Union and the Ministry of Science, Innovation and Universities.

reference letter bibliographic

- Molecular Therapy. 2025 Mar 5;33(3):895-916. doi:10.1016/j.ymthe.2025.01.049.