New advances in the improvement of the design of drugs against glial globular tauopathy

José Antonio del Río, principal investigator at the Institute for Bioengineering of Catalonia (IBEC) together with Dr. Isidre Ferrer from Bellvitge Biomedical Research Institute (IDIBELL) led a study where they have unraveled that the pathology shown by patients with Globular Glial Tauopathy is due to the generation of harmful protein deposits for neurons and glial cells.

Tauopathies are characterized by the accumulation of phosphorylated tau protein, that associates with phosphate groups.

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This accumulation causes protein dysfunction and ends up damaging the cells. Within this group of diseases, we find glial globular taupathy, such as Alzheimer’s, which are distinguished by the agglomeration of phosphor-tau protein in neurons, forming aggregates in the glial cells.

This study shows that not only tau is responsible for these pathologies as previously believed, but that many other proteins are abnormally phosphorylated, which leads to the formation of these protein deposits. These findings also demonstrate that these accumulations not only affect neurons, but also the accompanying glial cells, which can lead to the dysfunction of neuronal connections. In addition, these aggregates can move from one neuron to another, causing the spread of damage to healthy cells, as if it were an infection.

To carry out the study, several patients’ cases with this type of tauopathy have been analysed, thanks to the participation of the Hospital of Navarra, which has been responsible for performing the proteomic and phosphorylation analysis.

These findings open a new research path for the design of new drugs that stop disease progression. To do this, we must first take into account that the addition of phosphate groups not only affects tau, but also other proteins and, on the other hand, not only neurons but also glial cells are involved, which also favours transmission and disease expansion.

This study was supported by Ministry of Economy and Competiveness, “La Caixa Fundation” and European Regional Development Fund.


Reference article: Isidro Ferrer, Pol Andrés-Benito, Maria Victoria Zelaya, Maria Elena Erro Aguirre, Margarita Carmona, Karina Ausín, Mercedes Lachén-Montes, Joaquín Fernández-Irigoyen, Enrique Santamaría & José Antonio del Rio. Familial globular glial tauopathy linked to MAPT mutations: molecular neuropathology and seeding capacity of a prototypical mixed neuronal and glial tauopathyActa Neuropathologica (2020) DOI: https://doi.org/10.1007/s00401-019-02122-9 

Source: IDIBELL