Molecular Neurobiology - Universidad Autónoma de Madrid

Molecular Neurobiology
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D2
Function of microtubular proteins in neurons
Research summary
Research summary
Staff
Publications
Other activities
Doctoral theses
Our main objectives are: to understand tau pathology in Alzheimer disease and to look for a therapeutical
use of ensheating olfactory cells as reparators of axonal damage. Tau pathology in those neurodegenerative
disorders is mainly due to its hyperphosphorylation and its aberrant aggregation, and, in the last two years,
we have done some experiments to know how those phosphorylation and aggregation processes take place.
In this way, we have determined a region in tau molecule that plays an important role in those features
(phosphorylation and aggregation). In addition, we have suggested a novel mechanism; in which tau protein
could be involved, to explain the assembly of a pathological protein aggregate found in the brain of Alzheimer
disease patients, the Hirano body. On the other hand, we have continued our analyses on tau phosphorylation
by protein kinase GSK3, we have found, during GSK3 analysis, an activation of this enzyme, after an increase
of intracellular calcium. In a study carried out by F. Hernández, it has been shown that an increase in intracellular
calcium results in the activation of calpain, a protein that cleaves GSK3 removing its aminoterminal region and,
as result of that, the kinase is activated.
Also, we have described that tau protein, in extracellular form, may play a role in the tau pathology propagation,
in Alzheimer disease. Our data suggest that upon neurondegeneration, intracellular tau becomes extracellular
tau, and this extracellular protein can bind to cellular receptors (muscarinic receptors M1 and M3). As a
consequence of that an increase in intracellular calcium could occur. This calcium increase could be toxic for
the cell.
About our studies on ensheating olfactory glia cells as reparators of axonal damage, we have immortalized
these cells and studied their functionally after immortalization and desinmmortalization. These studies are
related to the possible future therapeutical use of these cells.
Awards
CBM 2007-2008