Brain's Protective Response Delays Huntington's Symptoms
Author: University of Western Ontario
Published: 2010/02/23 - Updated: 2025/12/15
Publication Details: Peer-Reviewed, Research, Study, Analysis
Category Topic: Neurological Disorders - Related Publications
Page Content: Synopsis - Introduction - Main - Insights, Updates
Synopsis: This research reports findings from The Journal of Neuroscience on a protective mechanism that helps explain why Huntington's disease symptoms appear later in life despite patients being born with the mutated huntingtin protein. Scientists at Robarts Research Institute discovered that metabotropic glutamate receptors in the brain actively compensate for the disease's effects during early stages, modifying cell signaling to protect against neurodegeneration. As people age, this protective compensation diminishes, leading to the characteristic late-onset symptoms. The work is particularly valuable because it identifies specific biological targets - the glutamate receptors - that could lead to therapeutic interventions for a condition that currently has no treatment to slow or stop its progression. For families affected by this dominant genetic disease, where each child of an affected parent faces a 50 percent inheritance risk, understanding these protective pathways represents meaningful progress toward eventually developing drugs that could extend the brain's natural defense mechanisms and delay or reduce the devastating physical and mental deterioration that defines Huntington's - Disabled World (DW).
Introduction
Protecting the Brain from Huntington's Disease
Because HD is a dominant genetic disease, every child with an affected parent has a 50 percent chance of inheriting the fatal condition.
Huntington's disease (HD) is a cruel, hereditary condition that leads to severe physical and mental deterioration, psychiatric problems and eventually, death. Currently, there are no treatments to slow down or stop it. HD sufferers are born with the disease although they do not show symptoms until late in life.
Main Content
In a new study published in The Journal of Neuroscience , Stephen Ferguson and Fabiola Ribeiro of Robarts Research Institute at The University of Western Ontario identified a protective pathway in the brain that may explain why HD symptoms take so long to appear. The findings could also lead to new treatments for HD.
The symptoms of Huntington's disease are caused by cell death in specific regions of the brain. Patients who have HD are born with a mutated version of the protein huntingtin (Htt), which is thought to cause these toxic effects. While researchers know HD results from this single, mutated protein, no one seems to know exactly what it does, why it does not cause symptoms until later in life, or why it kills a specific set of brain cells, even though Htt is found in every single cell in the human body.
Ferguson and Ribeiro used a genetically-modified mouse model of HD to look at the effects of mutated Htt on the brain.
"We found there was some kind of compensation going on early in the life of these mice that was helping to protect them from the development of the disease," says Ferguson, director of the Molecular Brain Research Group at Robarts, and a professor in the Department of Physiology & Pharmacology at Western's Schulich School of Medicine and Dentistry. "As they age, they lose this compensation and the associated protective effects, which could explain the late onset of the disease."
Ferguson adds that metabotropic glutamate receptors (mGluRs), which are responsible for communication between brain cells, play an important role in these protective effects. By interacting with the mutant Htt protein, mGluRs change the way the brain signals in the early stages of HD in an attempt to offset the disease, and save the brain from cell death. As a result, mGluRs could offer a drug target for HD treatment.
Because HD is a dominant genetic disease, every child with an affected parent has a 50 percent chance of inheriting the fatal condition.
This research, funded by the Canadian Institutes of Health Research, sheds light on the onset of HD and the potential role of a mutant protein in patients, paving the way for the development of new drug therapies.
Insights, Analysis, and Developments
Editorial Note: What makes this discovery particularly compelling is how it reframes our understanding of Huntington's disease not as a straightforward march toward neurodegeneration, but as an active biological struggle where the brain fights back for years before succumbing. The fact that metabotropic glutamate receptors - which normally facilitate routine communication between neurons - can be co-opted into a protective role suggests the brain has more adaptive capacity than previously recognized. This opens an intriguing therapeutic window: if researchers can pharmacologically enhance or prolong these natural compensatory mechanisms, they might push symptom onset further into old age or reduce severity when symptoms do emerge. For a disease that has resisted treatment precisely because we didn't understand why the ubiquitous mutant protein selectively destroys certain brain regions while sparing others, identifying the molecular players in this delayed onset represents the kind of fundamental insight that precedes genuine therapeutic breakthroughs - Disabled World (DW).Attribution/Source(s): This peer reviewed publication was selected for publishing by the editors of Disabled World (DW) due to its relevance to the disability community. Originally authored by University of Western Ontario and published on 2010/02/23, this content may have been edited for style, clarity, or brevity.