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2011 Grants - Rossi
The Role of Tau in Chromosome Stability and Its Link to Neurodegeneration
Giacomina Rossi, Ph.D.
Foundation Carlo Besta Neurological Institute
2011 New Investigator Research Grant
Tau is a protein that normally helps to stabilize cell structure and assist in the transport of nutrients within cells. In Alzheimer's disease and some related conditions such as frontotemporal lobe degeneration (FTLD), tau behaves abnormally, forming pathologic structures such as neurofibrillary tangles that are characteristic features of these diseases.
About 20 percent of cases of FTLD are caused by inherited genetic mutations, and some of these are caused by known mutations in the gene that codes for the tau protein. Giacomina Rossi, Ph.D. and colleagues have also shown that people who have FTLD and genetic mutations of tau also have abnormal chromosomes in certain cell types. Chromosomes are organized structures of the genetic material (DNA) in a cell's nucleus that form during cell division. The finding that tau mutations lead to abnormal chromosomes suggests that tau is also important for maintaining the stability of these structures and the integrity of the genetic material.
Dr. Rossi and colleagues have proposed to characterize the mechanisms by which mutations in tau lead to chromosomal abnormalities. These studies will examine the chromosomes of lymphocytes and fibroblasts, which are non-nerve cells in the brain in which tau mutations have been shown to cause chromosomal abnormalities. The researchers will also use mice carrying tau mutations to determine how these mutations cause chromosomal abnormalities, and how those abnormalities lead to neurodegeneration in the brain. These studies may help to define potential targets for therapies to halt the damage to nerve cells caused by mutations of tau.