Pyk2 deficits contribute to memory problems in Huntington’s disease mouse model

Researchers from the Institute of Neurosciences of the UB and from IDIBAPS together with a team from the University Pierre and Marie Curie (UPMC, France) and the Institute du Fer à Moulin, published a study in Nature Communications, which demonstrates that the regulation in Pyk2, a protein-tyrosine kinase, causes alterations of the synaptic plasticity involved in memory tasks, associated with the hippocampus in mouse models of neurodegenerative diseases, such as Huntington's.

The study was co-led by the team of Sílvia Ginés and Jordi Alberch, from the Institute of Neurosciences of the UB, IDIBAPS, both members of the Biomedical Research Networking Centres in Neurodegenerative Diseases (CIBERNED), and the group led by J. A Girault, from UPMC. The study also has the participation of the UB researcher Verònica Brito, and UPMC researcher Albert Giralt, who will soon join the UB.

According to Sílvia Ginés, "so far, we knew that Pyk2 protein was activated by calcium with a distinguished expression in the hippocampus where it has an important role as regulator of synaptic plasticity and therefore in the controlling process of memory creation and consolidation". Also, she said that "however, most of the projects, which described the function of Pyk2, were conducted in culture cells, that is, in vitro systems, and there was not much information about its in vivo function". The researcher notes that this new study "describes for the first time the functional importance of Pyk2 in the hippocampus as a regulator of the dynamics of dendritic spines, essential structures for synaptic plasticity and thus for the memory processes, especially through the activity modulation in the NMDA receptor and PSD96 protein".

The study also shows the activity of Pyk2 at a pre-synaptic level and the electron microscopy experiments show the presence of Pyk2 in nerve terminals that previous biochemical observations have confirmed. Also, when there was a lack of Pyk2, the length of the dendritic spine decreased both in vivo and in vitro.

In this study, researchers tested the effects of Pyk2 deficit in a mouse model with Huntington's disease. In this neurodegenerative disease, apart from motor alterations, there are other highly disabling cognitive alterations, in the first stages of the disease. "In this study, we showed that Pyk2 deficits contribute to memory problems in a determining way" says Jordi Alberch.

Moreover, alterations in memory processes are common in other neurodegenerative diseases, such as Alzheimer's disease, Parkinson's or others. "Pyk2 regulating these cognitive processes through different mechanisms (NMDA receptors, dendritic spines), makes Pyk2 to be a therapeutic target for the treatment of Huntington's and other neurodegenerative diseases" concluded Gines.