Context

The functional diversity of microtubules is due to the various and numerous post-translational modifications (PTM) that affect tublins. Known PTMs include acetylation, polyglutamylation, polyglycation, phosphorylation, and tyrosination/detyrosination cycles. These modifications have an impact on microtubule dynamics, their organization, and their interactions with other cellular compounds and compartments. The tyrosination/detyrosination cycle is particularly involved with microtubule regulation in the neural cells, muscle cells, and dividing cells.

Benefits

Responsible for detyrosination, this enzymatic activity is carried by TCPase proteins for Tubulin carboxypeptidase. While the existence of TCPases has been known for more than 40 years, they have never been identified until now. Thanks to an innovative biometric approach, the IGH research team has identified and validated a TCPase, and has developed new reversible and irreversible inhibitors for this protein’s enzymatic activity.

Applications

Primary: Therapy for neurodegenerative pathologies, particularly Tauopathies. Secondary: Therapy for muscular dystrophy; oncology therapy.