Molecular and Cellular Bases of Neurodegeneration

The objective of our laboratory is to determine the cellular and molecular mechanisms that cause neuron death in neurodegenerative diseases that affect the basal ganglia (Parkinson's disease, Huntington's disease, etc.). By understanding these mechanisms, we hope to identify therapeutic targets for the treatment of these diseases, for which no cure currently exists.

Specifically, we are interested in identifying ɑ-synuclein-dependent molecular mechanisms of neurodegeneration. This protein plays a key role in neurodegeneration. Ɑ-synuclein is predominantly located in the presynaptic neuron terminals. Its anomalous accumulation in intramural structures called Lewy bodies is the pathological signature of neurodegenerative disease grouped together with the name of synucleinopathies, and which include Parkinson's disease and Lewy body dementia. Furthermore, mutations in the ɑ-synuclein gene cause autosomal-dominant forms of synucleinopathy. However, the cellular and molecular mechanisms by which ɑ-synuclein causes the death of specific populations of neurons are unknown.

The main projects of the laboratory to the following:

  1. Study of the role of the expression, aggregation and post-translational modifications of ɑ-synuclein in neuron death.

  2. Study of the implication of cellular signaling pathways such as the unfolded protein response (UPR), and protein breakdown (proteosomal / lysosomal pathways) in neurodegeneration.  

To achieve this, we use a methodology developed in our laboratory based on automated microscopy, which allows us to perform analyses such as longitudinal studies of neuron survival and generation of regression models for identifying explanatory/predictive variables of neuron death, in vivo stability studies of proteins using optical pulse-chase methodology, protein visualization, mRNA and activation of cell pathways of interest by means of fluorescent reporters.



Dra. Montserrat Arrasate

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Contact

Contact:
Cristina Canciani
Avda. Pío XII, 53
31008 Pamplona
Spain

(+34) 948 194 700 Ext. 2013
canciani@unav.es