Researchers have discovered that suppressing a nucleolar complex can reduce Alzheimer’s-related protein toxicity.
Scientists have identified a key nucleolar complex that could be instrumental in combating neurodegenerative diseases. This complex plays a critical role in maintaining cellular health by regulating protein homeostasis (proteostasis)—the process by which cells ensure proper protein balance and function.
Research reveals that suppressing this nucleolar complex significantly reduces the toxic effects of proteins associated with Alzheimer’s disease. This suppression enhances the cell’s natural defenses by promoting the degradation of harmful proteins. The mechanism works by regulating proteostasis across tissues through the modulation of TGF-β signaling, a pathway essential for cell growth, differentiation, and maintaining tissue health.
This breakthrough opens exciting new possibilities for the development of new therapies that could slow or even prevent diseases like Alzheimer’s, offering hope for a future of healthy aging.
The Decline of Proteostasis and Neurodegenerative Diseases
As we age, the intricate balance of protein homeostasis (proteostasis) — the system responsible for maintaining cellular health by ensuring proteins are correctly folded— begins to falter. This decline leads to the accumulation of toxic protein aggregates, a hallmark and an underlying cause of neurodegenerative diseases such as Alzheimer’s disease.
A new study led by Hebrew University researchers Prof. Ehud Cohen and the student Huadong Zhu from the Department of Biochemistry and Molecular Biology at the Institute for Medical Research Israel–Canada (IMRIC) in collaboration with the lab of Dr. Yonatan Tzur of the Alexander Silberman institute of Life Science, sheds light on a promising new way to address this issue, with implications that extend far beyond basic research.
The research identifies that a nucleolar complex, FIB-1-NOL-56, is a central player in the regulation of proteostasis at the cellular and organismal levels. By suppressing the activity of this complex, the team observed a marked reduction in the toxic effects of Alzheimer’s-associated Aβ peptide and another disease-causing protein, in model organisms. This discovery not only deepens our understanding of how the body manages cellular stress but also offers hope for future treatments that could delay or prevent a myriad of devastating neurodegenerative diseases.
Hope for Future Treatments
“Our findings go beyond the lab bench,” explains Prof. Cohen. “Neurodegenerative diseases affect millions of people worldwide, impacting families and caregivers. By uncovering how cells communicate to maintain protein integrity, we’re opening the door to the development of preventive therapeutic approaches that could delay disease onset and significantly improve the quality of life of the elderly.”
This research has a real-world relevance that’s hard to ignore. Neurodegenerative diseases like Alzheimer’s disease touch nearly every family, affecting not just patients but also their loved ones. The ability to slow or prevent these conditions could mean more meaningful moments with aging parents, fewer health crises, and a longer period of independence for millions of older adults.
As the team looks ahead to translating these discoveries into treatments, the potential to improve the lives of countless individuals grows ever clearer. With continued research, this approach could lead to a future where aging does not come hand-in-hand with the specter of neurodegenerative disease.
Reference: “A nucleolar mechanism suppresses organismal proteostasis by modulating TGFβ/ERK signalling” by Huadong Zhu, Reut Bruck-Haimson, Adam Zaretsky, Irit Cohen, Roni Falk, Hanna Achache, Yonatan B. Tzur and Ehud Cohen, 3 January 2025, Nature Cell Biology.
DOI: 10.1038/s41556-024-01564-y
