Frontotemporal dementia is projected to account for about 10-15% of all dementia cases in the United States, with the greater part of patients only living an average of 6-8 years following diagnosis. But in a new research, investigators from the University of Alabama at Birmingham say they may have revealed a potential drug target for the condition.
Frontotemporal dementia (FTD) is indicated by fast deterioration of language skills, motion and modifications in character, behavior and social skills. Onset of FTD very generally takes place while in mid-late 50s – considerably earlier than the normal age of Alzheimer’s disease onset.
FTD is considered to be activated by cell damage in the frontal or temporal lobes of the brain. Even though it is not clear accurately what leads to this cell damage, earlier research have suggested that it may be triggered by mutations in genes that express a protein known as tau; an accumulation of tau has also been related with Alzheimer’s.
But the investigators of this recent research – lead by Dr. Erik Roberson, note that small is identified about how tau mutations impact certain brain regions, resulting in FTD.
NMDA receptor recognized as drug target for FTD
To figure out more, Dr. Roberson and his team examined novel mouse models that possessed a mutated human tau gene and shown behaviors identical to those identified in humans with FTD.
Outcomes of the research – presented in The Journal of Neuroscience – exposed that the mutant tau present in the mouse models interrupted with associations between neurons – known as synapses – by reducing the size of anchoring sites for NMDA receptors essential for brain signaling.
“Decrease of the anchoring sites left fewer NMDA receptors accessible at the synapse to get excitatory signals, thus restricting synaptic firing and network activity,” describes Dr. Roberson.
Subsequent, the team examined the results of an existing medicine permitted by the Food and Drug Administration (FDA) – cycloserine – in the mouse models. Cycloserine – an antibiotic generally recommended for tuberculosis – is recognized to enhance the function of NMDA receptors.
The investigators identified that cycloserine was capable to raise NMDA receptor function in the mouse models, which renewed synaptic signaling and reversed FTD-associated behaviors.
Leaving comments on the team’s results, Dr. Roberson says:
“This study offers mechanistic understanding into how a tau mutation affects particular brain areas to damage a network. It also offers a possible therapeutic target, the NMDA receptor, which seems to be correct the network and behavioral irregularities.”
The scientists say their results suggest that enhancing NMDA receptor function could possibly treat mankind with FTD.
In addition, even though their results have to be proved with further animal research, the team states that cycloserine could be used to enhance NMDA receptor function in human studies.