The enzyme JNK3 was previously known only as a molecular target in degenerative processes. However, it has now also been identified in plasma as an indicator of neuronal damage, paving the way for new diagnostic and clinical applications.

The research, published in Nature Parkinson's Disease, is coordinated by Tiziana Borsello, professor at the University of Milan, head of the Laboratorio Morte neuronale e neuroprotezione at the Mario Negri IRCCS Institute for Pharmacological Research and founder of the University of Milan spin-off PepTiDa. It is the result of an interdisciplinary collaboration with Domenico Raimondo of Sapienza University of Rome, Mariaelena Repici of Aston University UK, Nunzio Perta of the Università Politecnica delle Marche and Mario Negri IRCCS, and Giorgia Melli of the Università della Svizzera Italiana.

‘These results represent a breakthrough in understanding Parkinson's and neurodegenerative diseases. JNK3, previously known as a crucial molecular target in degenerative processes, is now emerging as a new biomarker, capable of guiding early diagnosis, monitoring disease progression and potentially opening up new therapeutic avenues,’ says Tiziana Borsello, professor at the Rodolfo Paoletti Department of Pharmacological and Biomolecular Sciences at the Università Statale di Milano and head of the Laboratorio Morte neuronale e neuroprotezione at the Mario Negri Institute whose research group was among the first to hypothesise that JNK3 could represent not only a therapeutic target but also a tangible sign of neuronal dysfunction.

This insight took concrete form thanks to collaboration with Giorgia Melli's group, which provided a carefully selected cohort of patients to test the hypothesis in a clinical setting, successfully translating the biology of JNK3 from laboratory research to clinical research for the first time, and thus building a relationship between scientific experimentation and concrete medical applications.

The collaborative efforts of the entire team have led to a more comprehensive understanding of the pathological mechanisms underlying degenerative neurological diseases. JNK3 has emerged as a new blood biomarker associated with neurodegeneration. It demonstrates a high level of specificity in distinguishing between patients with Parkinson's disease and healthy individuals, can be detected through a straightforward blood test and is therefore potentially useful for facilitating the early diagnosis of the disease, as well as for patient stratification and selection for clinical trials.

‘This discovery is part of a broader vision: understanding how stress responses, dysfunction and neuronal vulnerability intertwine in various brain diseases, whether chronic, such as Parkinson's and Alzheimer's, or acute, such as cerebral ischaemia,’ adds Domenico Raimondo of the Department of Molecular Medicine at Sapienza University.

‘Biomarkers such as JNK3, together with innovative therapeutic strategies, will accelerate clinical translation and pave the way for personalised medicine for patients with brain diseases. To this end, we founded PepTiDa, an innovative start-up and spin-off of the University of Milan,’  concludes Tiziana Borsello.

Further Information

Domenico Raimondo, Department of Molecular Medicine, Sapienza University of Rome
Laboratory affiliated with the Pasteur Institute Italy - Cenci Bolognetti Foundation

domenico.raimondo@uniroma1.it