A tiny molecular tag that helps our immune system fight bacteria has just been caught doing something nobody expected: putting a "dispose of this" label on faulty sugar stores in the brain. And that quiet act of cellular housekeeping could one day save the lives of young people struck by a fatal brain disease.
The discovery comes from scientists at the University of Cambridge and the MRC Laboratory of Molecular Biology, who published their findings this week in the journal Nature. Led by Professor Felix Randow, the team found that a protein called RNF213 patrols the brain looking for abnormal glycogen — the form in which cells stockpile glucose for energy. When glycogen is built incorrectly, it turns into dense, insoluble lumps called polyglucosan bodies. Over time these toxic clumps pile up inside brain cellscars neurons and cause irreversible tissue damage.
Here is where RNF213 steps in. It reaches out and attaches a small tag called ubiquitin directly to the defective glycogen. That tag works like a giant red warning sticker reading "take out the trash," triggering a cellular recycling process known as autophagy to sweep the damaged energy stores away and break them down.
The finding is remarkable for a simple reason. Ubiquitin was thought to be a specialist that only marked proteins for recycling. "It is remarkable to see the same enzyme fighting bacteria and policing glycogen," said Randow, who a few years ago discovered that RNF213 also tags a molecule called LPS on intracellular bacteria to mark them for destruction. Now the team has shown that ubiquitin can directly label carbohydrates too — a fundamental shift in how scientists understand the body's quality-control systems.
That matters deeply for a rare and cruel disease. Lafora disease is an inherited neurological condition first identified in 1911 by Spanish neurologist Gonzalo Rodríguez Lafora. It usually begins during adolescence, when toxic sugar deposits known as Lafora bodies accumulate in the brainaisseur gradually worsen. Over time, patients suffer increasingly severe seizures, rapid cognitive decline and loss of motor control. The disease is ultimately fatal, and after more than a century of medical awareness it remains incurable. Existing treatments only manage symptoms.
"This cleanup pathway is crucial for addressing rare genetic disorders such as Lafora disease and polyglucosan body myopathy," the researchers note. By understanding exactly how RNF213 marks faulty glycogen and sends it for destruction, scientists gain a new window into how healthy cells keep their energy stores clean — and a possible path toward therapies that help the brain clear these toxic deposits before they cause harm.
First author Matthew Yip, a postdoc at the MRC Laboratory of Molecular Biology, summed up the wider promise: "We are beginning to realize that ubiquitylation extends far beyond proteins. It is exciting to see what new biological roles emerge in the future."
The road from a lab discovery to a cure for a century-old disease is long. But for the first time, researchers have found a specific, natural mechanism the brain uses to police its own sugar storage — a discovery that turns a once-hopeless disease into a problem with a new set of doors waiting to be opened.