Summary: A recent study has shown that troriluzole can prevent early-stage brain changes in a mouse model of Alzheimer’s disease. The research demonstrated that troriluzole reduces harmful glutamate levels, preserving memory and cognitive function.
This breakthrough suggests that early intervention with troriluzole could slow or even halt the progression of Alzheimer’s, offering new hope for potential treatments. However, further studies are necessary to determine its effectiveness across different stages of the disease.
Key Facts:
- Troriluzole reduces harmful glutamate levels, protecting brain function.
- Mice treated with troriluzole showed improved memory and learning abilities.
- Further research is needed to explore troriluzole’s effects across all stages of Alzheimer’s.
Source: Auburn University
In a recent development in Alzheimer’s disease research, Auburn University scientists have studied a new drug, troriluzole, that can prevent brain changes leading to memory loss and cognitive decline in a mouse model of the disease.
This study, recently published in the Journal of Neurochemistry, is the first to show how troriluzole can target early-stage alterations associated with Alzheimer’s, providing new hope for potential treatments.
Dr. Miranda Reed, a Professor in the department of Drug Discovery at Auburn University and Delivery and the studies main researcher, noted that “by examining how drug treatments can intervene early in the disease process, we aim to develop therapies that might prevent or even cure Alzheimer’s.”
“This study also highlights how scientific advancements can transform our understanding of complex diseases like Alzheimer’s,” said Dr. Michael Gramlich, an Assistant Professor of Biophysics and the study’s other main researcher.
Breaking New Ground in Alzheimer’s Research
Alzheimer’s disease affects millions of people worldwide, causing progressive memory loss, confusion, and eventually the inability to perform basic tasks. Despite decades of research, a cure remains elusive. Alzheimer’s is characterized by the accumulation of amyloid plaques and tau tangles in the brain, which disrupt neural communication. In the early stages, excessive levels of the neurotransmitter glutamate cause damaging overactivity in synapses, the connections between nerve cells.
The study conducted by Auburn University researchers, led by Drs. Miranda Reed and Michael Gramlich, investigated how troriluzole, a novel drug, can maintain normal brain function in mice genetically modified to replicate early Alzheimer’s stages. The results are compelling: troriluzole not only reduced harmful glutamate levels but also improved memory and learning in the mice, suggesting a maintenance of healthy brain function.
“Our research demonstrates that by targeting synaptic activity early, we may be able to prevent or slow the progression of Alzheimer’s. This could revolutionize the way we approach treatment for this disease,” noted both researchers.
How Troriluzole Works
In the Auburn study, mice treated with troriluzole showed a significant reduction in synaptic glutamate levels and decreased brain hyperactivity. These molecular changes led to tangible improvements: the treated mice performed better in memory tests, such as navigating mazes, indicating that their cognitive functions were restored.
“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,” said Dr. Reed. “It’s like repairing an engine before it fails completely.”
A Collaborative Effort with Wide Implications
This research was a collaborative effort involving Auburn University’s College of Science and Mathematics, the Harrison College of Pharmacy, and the Center for Neuroscience Initiative, along with private researchers and students. The team’s combined expertise in neuroscience and pharmacology was crucial to the study’s success.
“This collaboration blends basic science and pharmaceutical research to tackle one of the most challenging neurological issues of our time,” Dr. Gramlich emphasized. “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.”
What’s Next?
While the results in mice are encouraging, the researchers emphasize the need for further studies to determine how troriluzole works at different stages of disease progression.
About this neuropharmacology and Alzheimer’s disease research news
Author: Mary Prater
Source: Auburn University
Contact: Mary Prater – Auburn University
Image: The image is credited to Neuroscience News
Original Research: Closed access.
“Troriluzole rescues glutamatergic deficits, amyloid and tau pathology, and synaptic and memory impairments in 3xTg-AD mice” by Michael Gramlich et al. Journal of Neurochemistry
Abstract
Troriluzole rescues glutamatergic deficits, amyloid and tau pathology, and synaptic and memory impairments in 3xTg-AD mice
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.
