Drug Can Reverse Harmful Gene Changes In Alzheimer’s

Posted on 4 May 2016

The neurotransmitter glutamate accumulates in both aging and Alzheimer’s disease, but treatment with riluzole could reverse these associated genetic changes

Glutamate is an essential molecule used as a neurotransmitter to transmit signals through your synapses. It’s used to transmit excitatory signals and is usually tightly controlled, as it’s damaging to neurons in large concentrations. Unfortunately in both aging and Alzheimer’s, this control becomes dysregulated, and glutamate can end up accumulating in places where it’s not meant to be. This causes harm, and even death to neighbouring neurons. 

“In aging and Alzheimer’s, the chemical signal glutamate can accumulate between neurons, damaging the circuitry. When we treated rats with riluzole, we saw a suite of changes. Perhaps most significantly, expression of molecules responsible for clearing excess glutamate returned to more youthful levels”

Modulating glutamate levels

New research attempted to study the aging glutamate system using a drug called riluzole, which is known to affect glutamate. Curiously, when this drug was applied to elderly rats or a rat model of Alzheimer’s, it appeared to trigger ‘youth promoting’ changes in the hippocampus – the section of the brain responsible for encoding long term memories.

One closer inspection, riluzole was able to modify particular gene expression associated with the glutamate system.  This included a gene called EAAT2 which helps remove excess glutamate and its declining activity is implicated in both aging and Alzheimer’s. Riluzole was able to switch EAAT2 back on in these rats, restoring it to a more youthful profile. 

The hippocampus (red) is an important therapeutic target and its function declines as you age

The hippocampus (red) is an important therapeutic target and its function declines as you age

Another new treatment

When it comes to aging and Alzheimer’s it’s unlikely one drug is going to fix everything, but with further study a drug like riluzole could prove to be a handy addition to the current repertoire. Riluzole is also already approved for treatment of amyotrophic lateral sclerosis (ALS) which means it could be introduced relatively quickly. 

“We hope to use a medication to break the cycle of toxicity by which glutamate can damage the neurons that use it as a neurotransmitter, and our studies so far suggest that riluzole may be able to accomplish this. We found that in addition to recovering the expression of EAAT2, the drug restored genes critical for neural communication and plasticity, both of which decline with aging and even more significantly in Alzheimer’s disease”

Read more at MedicalXpress

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