Italian researchers have discovered a
new gene that causes Alzheimer's Disease, according to a new
study out Sunday.
The result is the fruit of the collaboration of several Italian
research groups, engaged for years in the study of the genetic
causes of the disease, coordinated by the Molinette hospital of
the Città della Salute of Turin.
The discovery, published in the international scientific journal
Alzheimer's Research & Therapy, "suggests the role of rare
genetic mutations also as a cause of the disease in old age",
explains Innocenzo Rainero who directs the Alzheimer's and
related dementia Center of the Molinette hospital and the
University of Turin.
The scientific group, coordinated by Dr. Elisa Rubino,
researcher at the Alzheimer's Disease Center of Molinette,
studied for several years an Italian family with senile-onset
Alzheimer's disease, discovering that it was caused by mutations
in the Grin2C gene, a gene that codes for a subunit of the Nmda
glutamate receptor.
This was achieved through the use of advanced molecular genetic
techniques.
Furthermore, it was possible to demonstrate the effects that
this mutation causes in cellular models by increasing neuronal
excitability and altering the binding of this protein with other
neuronal proteins.
"Until now, rare mutations in the Psen1, Psen2 and App genes
were known to cause Alzheimer's disease, mainly in presenile
age", comments Rainero, who had already contributed to the
identification of Psen1 in 1995.
"We expect Grin2C to be a very rare cause of Alzheimer's
disease," explains Rubino, emphasizing that "however, the most
significant aspect of the research is the confirmation of the
role that glutamate-related excitotoxicity mechanisms may have
in the development of the disease.
When glutamate interacts with the Nmda receptor on neurons, a
channel opens that promotes the entry of calcium ions.
If this stimulation is excessive, it causes intense excitation
of the neuron that leads to cell death."
From a clinical point of view, it is particularly interesting to
note how, before the development of cognitive deficit, patients
carrying the mutation have developed a depressive mood disorder
for years, say the researchers.
The new study, they note, "will require the development of new
drugs capable of reducing glutamate-induced cerebral
excitotoxicity to slow the progression of this dramatic
disease."
The research was carried out in collaboration with Elisa Giorgio
of the Department of Molecular Medicine at the University of
Pavia, with Alfredo Brusco of the Department of Neuroscience at
the University of Turin and with Fabrizio Gardoni of the
Department of Pharmacology and Biomolecular Sciences at the
University of Milan.
Alzheimer's is the main cause of serious cognitive deficits and
has become one of the major health problems worldwide.
Scientific research has shown that the disease is the result of
a complex interaction between genetic factors and numerous
environmental factors, such as hypertension, obesity, diabetes,
depression and social isolation that favor the deposition in the
brain of two toxic proteins, beta amyloid and tau protein,
responsible for neurodegeneration.
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