It was found that harmful glutamate levels were reduced by troriluzole, while cognitive functions showed improvement.
A novel drug has been found to rescue memory loss in a mouse model of Alzheimer’s disease, marking a recent breakthrough in research. Scientists at Auburn University have studied troriluzole, which has been shown to prevent brain changes that lead to memory loss and cognitive decline. Published in the Journal of Neurochemistry, this study is the first to demonstrate how troriluzole targets early-stage alterations linked to Alzheimer’s, offering new hope for future treatments.
According to Dr. Miranda Reed, a Professor in the Department of Drug Discovery at Auburn University, “by examining how drug treatments can intervene early in the disease process, therapies that might prevent or even cure Alzheimer’s could be developed.”
Dr. Michael Gramlich, an Assistant Professor of Biophysics and co-researcher, emphasized that “this study also highlights how scientific advancements can transform the understanding of complex diseases like Alzheimer’s.”
Groundbreaking effects on Alzheimer’s disease have been observed, as millions are impacted by its progressive symptoms, including memory loss, confusion, and difficulty with basic tasks. Despite extensive research, a cure has yet to be discovered. Alzheimer’s is marked by the buildup of amyloid plaques and tau tangles in the brain, which interfere with neural communication. Early stages involve excessive glutamate levels, leading to damaging overactivity in synapses.
A study conducted by Auburn University researchers, led by Drs. Miranda Reed and Michael Gramlich, examined the effects of troriluzole, a novel drug, on mice genetically modified to mimic early Alzheimer’s. The findings are promising: troriluzole not only reduced harmful glutamate levels but also improved memory and learning, indicating the preservation of healthy brain function.
“Our research demonstrates that by targeting synaptic activity early, it may be possible to prevent or slow the progression of Alzheimer’s. This could revolutionize approaches to treatment.”
Drs. Miranda Reed and Michael Gramlich
The mechanism behind troriluzole’s effects was explored in a study at Auburn University, where treated mice exhibited a significant reduction in synaptic glutamate levels and decreased brain hyperactivity. These molecular changes translated into observable benefits, as the treated mice demonstrated improved performance in memory tests, such as maze navigation, indicating a restoration of cognitive functions.
“These findings are promising because they suggest that troriluzole can protect the brain at a fundamental level, starting with molecular changes and resulting in improved cognitive abilities. “It’s like repairing an engine before it fails completely.”
Dr. Miranda Reed
The impact of collaborative research has been demonstrated through a joint effort involving Auburn University’s College of Science and Mathematics, the Harrison College of Pharmacy, and the Center for Neuroscience Initiative, alongside private researchers and students. The study’s success was driven by the combined expertise in neuroscience and pharmacology.
“This collaboration blends basic science and pharmaceutical research to tackle one of the most challenging neurological issues of our time. “Our work not only enhances scientific understanding of Alzheimer’s disease but also offers a potential new treatment that could improve the lives of millions worldwide.”
Dr. Gramlich.
Looking ahead, while the results in mice are promising, further studies are needed to explore how troriluzole functions at various stages of disease progression.
https://doi.org/10.1111/jnc.16215
Abstract
Alzheimer’s disease (AD) is a neurodegenerative condition in which clinical symptoms are highly correlated with the loss of glutamatergic synapses. While later stages of AD are associated with markedly decreased glutamate levels due to neuronal loss, in the early stages, pathological accumulation of glutamate and hyperactivity contribute to AD pathology and cognitive dysfunction. There is increasing awareness that presynaptic dysfunction, particularly synaptic vesicle (SV) alterations, play a key role in mediating this early-stage hyperactivity. In the current study, we sought to determine whether the 3xTg mouse model of AD that exhibits both beta-amyloid (Aβ) and tau-related pathology would exhibit similar presynaptic changes as previously observed in amyloid or tau models separately. Hippocampal cultures from 3xTg mice were used to determine whether presynaptic vesicular glutamate transporters (VGlut) and glutamate are increased at the synaptic level while controlling for postsynaptic activity. We observed that 3xTg hippocampal cultures exhibited increased VGlut1 associated with an increase in glutamate release, similar to prior observations in cultures from tau mouse models. However, the SV pool size was also increased in 3xTg cultures, an effect not previously observed in tau mouse models but observed in Aβ models, suggesting the changes in pool size may be due to Aβ and not tau. Second, we sought to determine whether treatment with troriluzole, a novel 3rd generation tripeptide prodrug of the glutamate modulator riluzole, could reduce VGlut1 and glutamate release to restore cognitive deficits in 8-month-old 3xTg mice. Treatment with troriluzole reduced VGlut1 expression, decreased basal and evoked glutamate release, and restored cognitive deficits in 3xTg mice. Together, these findings suggest presynaptic alterations are early events in AD that represent potential targets for therapeutic intervention, and these results support the promise of glutamate-modulating drugs such as troriluzole in Alzheimer’s disease.