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LSA Fellows 8 

Project titel: Bassoon-associated Tauopathies: disease mechanisms and potential interventions

Project leader: Dr. Carolina Montenegro

    Montenegro mini


Neurodegenerative diseases are a heterogeneous group of diseases characterized by progressive degeneration of the structure and function of the nervous system. The clinical symptoms of these disorders are mainly characterized by alterations in mobility, cognitive losses and an increase in the recurrence of epileptic seizures. Despite the increase in incidence, these disorders currently have no cure, but only attenuation.

Tauopathies belong to this type of diseases, which include Alzheimer's disease (AD), Progressive Supranuclear Palsy (PSP), among others. Although some genetic alterations are related to tauopathies, the origin and development of this disease are still obscure. Therefore, it is crucial to find new genes and their role in the development of neurodegenerative disorders. This will help to better understand causes, mechanisms, diagnosis, and treatment of these diseases. The rationale of this project comes from the observation that mutations in the gene encoding the presynaptic protein Bassoon are associated with the etiology of PSP.

Here I propose to use neuronal cultures of mouse models to test, the mutations described in patients with PSP. The in vitro differentiation of these neurons will allow us to carry out an extensive and multidisciplinary analysis that includes the biochemical and functional evaluation of the synaptic activity and the mitochondrial integrity, together with the analysis of drugs that potentially interfere with the pathogenic processes.

The development of this project will contribute to understanding the molecular mechanism by which mutations in the Bassoon gene promote the generation of neurodegenerative diseases. Furthermore, we will obtain new knowledge about the pathophysiological processes of neuronal plasticity and potential concepts for their treatment.

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