Huntington's disease is a neurodegenerative disorder that causes involuntary movements, psychiatric disturbances, and dementia, caused by a mutation in the huntingtin gene (HTT) consisting of expansion of the number of repeats of a CAG (cytosine-adenine-guanine) triplet.
The role of the tau protein is associated with the operation of some components of the cytoskeleton (microtubules) responsible for the formation and maintenance of neuronal morphology and its connections. Alterations in tau protein are known in a number of neurodegenerative diseases, but untill now we were unaware that it plays a role in Huntington's disease.
An article published this week in the journal Nature Medicine, by CIBERNED researchers from the Center for Molecular Biology Severo Ochoa (CSIC-UAM) in collaboration with the group of CIBERNED the Institute of Biomedical Research of Bellvitge (IDIBELL) and VU University Medical Center, Amsterdam, describes that tau protein isoforms of subjects with Huntington's disease are similar to those produced in known tauopathies (frontotemporal dementia, Alzheimer's disease, progressive supranuclear palsy and corticobasal degeneration, etc.) causing an imbalance in the tau protein isoforms and deposits of hyper-phosphorylated tau in neurons and glial cells in the brain
Tau altered in several neurodegenerative diseases
As explained by one of the co-authors of the study, Isidre Ferrer, director of the Institute of Neuropathology IDIBELL and Chair at the University of Barcelona "in Huntington doesn't occur the same abnormal protein deposits hyper-phosphorylated tau in neurons that we observed in tauopathies known, but we could identify alterations in the different isoforms of tau protein in the brain and thus demonstrate that tau is also impaired in Huntington and in murine models of Huntington's disease.
Ferrer encompasses this discovery in a broader context which is the study of tau protein as a molecular target of several neurodegenerative diseases. "In any case, until now we thought we had to act in the process of formation of deposits of tau hyper-phosphorylated. Now we have seen that changes in tau are not always associated with these deposits hyperphosphorylated tau. Therefore treatments would have to be designed to modulate one step before, in the phase in which the formation of the different tau isoforms is produced by alternative splicing. "
Marta Fernández-Nogales, R Jorge Cabrera, Maria Santos-Galindo, Jeroen JM Hoozemans, Isidro Ferrer, Annemieke JM Rozemuller, Felix Hernandez, Jesus Avila and Jose J Lucas. "Huntington s disease is a four-repeat tau tauopathy with nuclear rods." Nature Medicine 2014