By TPS-IL • May 19, 2026
Jerusalem, 19 May, 2026 (TPS-IL) — Protein clumps long considered a hallmark of neurodegenerative diseases such as Huntington’s may actually represent a built-in defense system that helps brain cells survive stress and could open new avenues for future treatments, Israeli scientists said.
Researchers at the Hebrew University of Jerusalem are challenging decades of scientific assumptions that these structures, known as inclusion bodies, are primarily toxic byproducts responsible for killing neurons.
The scientists focused on Huntington’s disease, a hereditary neurodegenerative disorder caused by a genetic mutation that leads to the gradual breakdown of nerve cells in the brain. The disease affects movement, cognition and behavior, and currently has no cure. Treatment focuses on managing symptoms and improving quality of life.
Lead researcher Prof. Eran Meshorer told The Press Service of Israel that the protein clumps may function as a kind of biological “quarantine” system, isolating harmful proteins before they can damage the rest of the cell.
“The prevailing view in the field was that we need to fight those protein clusters,” Meshorer told TPS-IL. “The assumption has been that if we manage to eliminate them, we will be able to fight the disease itself. But we showed they actually protect the cells from dying, at least in the short term.”
The findings may carry implications for future drug development.
Many experimental therapies in neurodegenerative diseases have focused on removing protein aggregates from the brain. But Meshorer says that if these structures are actually protective, eliminating them could potentially interfere with the brain’s own defense mechanisms.
For years, visible protein aggregates in Huntington’s and similar disorders such as Alzheimer’s and Parkinson’s were widely viewed as evidence of cellular collapse and toxicity.
To investigate the role of the protein clumps, Meshorer’s graduate student Walaa Oweis developed a human cell model using stem cells derived from patients. The system allowed her to grow genetically identical “sister” neurons side by side, with some cells developing protein clusters while others did not.
The researchers then exposed the cells to stress conditions designed to mimic the pressures associated with neurodegenerative disease. The results showed a sharp difference in survival.
Neurons that did not form the protein clumps died at significantly higher rates, while cells containing the clusters proved far more resilient under stress.
According to Meshorer, the findings suggest the clumps may help protect neurons by trapping harmful misfolded proteins inside confined structures, preventing them from spreading through the cell.
The researchers also identified a protein called ATF3 as a central regulator in the process.
When ATF3 was removed, cells lost their ability to form the protective clumps and became much more vulnerable to stress. The study found that ATF3 directly activates genes linked to the cell’s “unfolded protein response,” a natural repair system activated when proteins become damaged or unstable.
The findings could significantly change how neurodegenerative diseases are treated. Rather than trying to eliminate protein clumps, future therapies might instead aim to enhance or fine-tune the brain’s natural defense systems, including ATF3 signaling and stress-response pathways.
Moreover, by focusing on strengthening neuronal survival mechanisms instead of simply removing aggregates, the study could also reshape drug development, biomarker research, and treatment strategies across multiple disorders such as Huntington’s, Alzheimer’s, and Parkinson’s.
Meshorer said that, through cooperation with pharmaceutical giant TEVA, he hopes to develop the therapeutic potential of ATF3.
“Future treatments, although it may take years to get there, may focus on strengthening pathways such as ATF3 that help cells cope with stress and maintain survival,” he said.
The study was published in the peer-reviewed journal Cell Death & Differentiation.
