{"id":9350,"date":"2026-06-06T12:04:15","date_gmt":"2026-06-06T12:04:15","guid":{"rendered":"https:\/\/news.theck1.no\/?p=9350"},"modified":"2026-06-06T12:04:15","modified_gmt":"2026-06-06T12:04:15","slug":"toxic-clumps-in-huntingtons-disease-may-protect-the-brain-too","status":"publish","type":"post","link":"https:\/\/news.theck1.no\/?p=9350","title":{"rendered":"Toxic Clumps in Huntington\u2019s Disease May Protect the Brain Too"},"content":{"rendered":"
\nSingularityHub – Shelly Fan<\/strong>
\n •
\nJune 5, 2026\n<\/div>\n\n
\n

The findings could lead to new treatments for multiple neurodegenerative diseases. <\/p>\n<\/div>\n

Huntington\u2019s disease is tragically predictable. An inherited genetic mutation causes neurons to make distorted, sticky proteins. These proteins clump together and gradually overwhelm brain cells. The brain loses its ability to learn, remember, and make decisions.<\/p>\n

This story is dogma in neuroscience. But decades of research and drugs targeting the clumps have had little success. Scientists are now wondering: Is there more to the story? In a twist, a team from the Hebrew University of Jerusalem and collaborators found<\/a> that protein clumps may be a neuron\u2019s first line of defense against damage.<\/p>\n

The misfolded or malfunctioning proteins are quarantined inside bubbly hubs called \u201cinclusion bodies.\u201d Often considered detrimental to cell health, disrupting their formation unexpectedly led to cells becoming more sensitive to stressors often seen in neurodegenerative diseases.<\/p>\n

Physical separation played just one part. Inclusion bodies also changed the activity of genes involved in neuroinflammation\u2014even in the absence of immune cells. Scouting the genetic landscape of cells derived from patients with severe Huntington\u2019s disease, the team homed in on a \u201cmaster regulator\u201d gene, ATF3, that orchestrates immune responses. Removing the gene lessened inclusion bodies\u2019 protective effects against damage in cultured cells.<\/p>\n

To be clear, the findings are only for a cell model of Huntington\u2019s disease in a petri dish. And inclusion bodies could be a double-edged sword: protective in the beginning and detrimental later on. Still, acknowledging them as a more complicated villain could better inform strategies for disorders that take over our minds like Huntington\u2019s.<\/p>\n

“Our results reveal\u2026that these structures are not merely byproducts of disease, but a central factor in the cell’s ability to mount a protective response against stress,\u201d said study author Eran Meshorer in a press release<\/a>.<\/p>\n

The Problem With PolyQ<\/h2>\n

It\u2019s long been believed that protein clumps in the brain gradually erode cognition. Whether they\u2019re the main driver of neurodegenerative disorders is still debated, but their presence accelerates brain cell injury, causing neurons to wither away.<\/p>\n

Alzheimer\u2019s disease, for example, is associated with two sets of protein clumps. One lives inside neurons (tau) and another gunks up the space between cells (amyloid). Decades of research aimed at removing amyloid clumps have met with minimal success, earning these doomed efforts the notorious nickname \u201cgraveyard of dreams.\u201d Despite their struggles, the FDA recently approved two major drugs that remove amyloid clumps and modestly slow cognitive decline, though the approval has been controversial<\/a> due to doubts about safety.<\/a><\/p>\n

Other untreatable neurodegenerative disorders also fall into this category. Clumps formed in Parkinson\u2019s disease erode the brain\u2019s ability to control movement, emotion, and even the perception of time<\/a>. Lou Gehrig’s disease, or ALS, produces inclusion bodies inside motor neurons, leading to muscle weakness and trouble swallowing. The disease eventually robs people of speech and motion.<\/p>\n

These diseases often have multiple genetic and environmental triggers. Huntington\u2019s, in contrast, is entirely genetic. The condition stems from the genome over-copying parts of the huntingtin gene (HTT<\/em>), which normally makes a key protein also called huntingtin.<\/p>\n

Normally, cells use the protein\u2019s large, stackable structure to build highways that transport all sorts of biological cargo, from molecules to organelles. The protein also plays an essential role during early brain development and neural wiring in adulthood.<\/p>\n

But a mutant form of the HTT<\/em> gene can wreak havoc. A common mutation, called polyQ expansion<\/a>, produces unwieldy, misfolded proteins. Nearly 30 years ago, researchers found that these errant proteins<\/a> aggregate inside parts of the cell. The clumps, or inclusion bodies, were widely thought to be detrimental. Some act like sticky tape that captures healthy proteins<\/a>, such as those involved in gene expression<\/a>, and torpedoes cellular health.<\/p>\n

But telltale signs<\/a> in cultured rat brain cells suggest a more nuanced story: Inclusion bodies could also be protective, sequestering mutant proteins as an early form of protection.<\/p>\n

A Tale of Two<\/h2>\n

The common factor in diseases featuring polyQ mutation is repetition. Mutated genes have long, duplicated sequences of the DNA letters cytosine, adenosine, and guanine (CAG). More CAG repeats in the genome translates into earlier disease onset.<\/p>\n

We all have this DNA triplet in our HTT<\/em> gene. But more than 39<\/a> repeats results in longer, toxic huntingtin proteins. Severe cases of Huntington\u2019s can feature over 100 CAG repeats, transforming the usually free-floating protein workers into sticky, dysfunctional layabouts.<\/p>\n

In the new study, the researchers first established a baseline. They used the gene editing tool<\/a> CRISPR-Cas9 to reduce CAG repeats in cells derived from Huntington\u2019s patients\u2014which carried over 180 copies\u2014to near normal levels.<\/p>\n

They then tagged the cells with a fluorescent marker that causes huntingtin proteins to glow bright green under the microscope. This let the team track protein aggregation in real time. Though they shared the same genetics, some cells formed inclusion bodies; others didn\u2019t.<\/p>\n

The team next challenged them with a chemical known to cause cellular stress. Those that formed clumps survived far more regularly than those that didn\u2019t. It was a \u201cstriking difference,\u201d the authors wrote. \u201cOnce a mutant PolyQ protein is expressed, the formation of IBs [inclusion bodies] protect[s] the cells rather than inflict[s] harm, at least short-term.\u201d<\/p>\n

Inflammation seems to be key. Although grown side-by-side, a genetic screen revealed cells with inclusion bodies were especially abundant in a gene called ATF3, which is known to regulate inflammation. Getting rid of the gene wiped out the neurons\u2019 ability to form inclusion bodies, making them more vulnerable.<\/p>\n

“Our results reveal a previously unknown role for ATF3 in orchestrating the formation of inclusion bodies in human neurons,\u201d said Meshorer.<\/p>\n

These are very early results. An immune molecule<\/a> bridges ATF3 and inflammation and is associated with Huntington\u2019s disease. Its levels are higher in patients with the condition. Increasing ATF3 activity could amp up the number of protective inclusion bodies and give neurons a fighting chance.<\/p>\n

The findings suggest inclusion bodies gather free-floating mutant proteins into clumps to protect neurons and reduce brain damage\u2014at least at the beginning of the disease. However, lab experiments rarely translate to treatments. How fast inclusion bodies form and when they begin to stress cells remains to be seen. Meanwhile, a gene therapy<\/a> for Huntington\u2019s is underway, and promising results in a small trial suggest an alternative path for treatment.<\/p>\n

Still, the study challenges the idea that protein clumps are always detrimental. If replicated in other neurodegenerative diseases such as Alzheimer\u2019s or ALS and if we can learn how long protection lasts, the results could pave the way for better-timed treatment that works with the body\u2019s protection, not against it.<\/p>\n

The post Toxic Clumps in Huntington’s Disease May Protect the Brain Too<\/a> appeared first on SingularityHub<\/a>.<\/p>\n

Read the full article →<\/a><\/p>\n","protected":false},"excerpt":{"rendered":"

SingularityHub – Shelly Fan • June 5, 2026 The findings could lead to new treatments for multiple neurodegenerative diseases. Huntington\u2019s disease is tragically predictable. An inherited genetic mutation causes neurons to make distorted, sticky proteins. These proteins clump together and gradually overwhelm brain cells. The brain loses its ability to learn, remember, and make decisions.<\/p>\n

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