Cologne Seminars on Ageing "The emerging roles of the nucleolus as an organismal proteostasis regulat"
- Date: Mar 20, 2025
- Time: 01:00 PM - 02:00 PM (Local Time Germany)
- Speaker: Ehud Cohen
- The School of Medicine of the Hebrew University, Jerusalem IL
- Location: MPI for Biology of Ageing
- Room: Auditorium
- Host: David Vilchez (CECAD)
About Ehud's talk:
The protein homeostasis (proteostasis) network encompasses a myriad of mechanisms that maintain the integrity of the proteome by controlling various biological functions, including protein folding and degradation. Early in life, this network efficiently maintains the integrity of the proteome; however, as the organism ages, its competence declines. This decline enables the aggregation of certain proteins and, in some cases, underlies the development of late-onset neurodegenerative disorders, such as Alzheimer’s disease. Accordingly, maintaining proteostasis through the later stages of life holds the promise of harnessing the mechanisms that protect young organisms to delay the emergence of these devastating diseases. Thus, a comprehensive characterization of proteostasis regulators is needed to assess the feasibility of this approach. Recent findings nominate the nucleolus as an organelle that, among other organelles, coordinates proteostasis across tissues. We discovered that knocking down the activity of the nucleolar FIB-1–NOL-56 complex protects model nematodes from the proteotoxicity of the Alzheimer’s disease-causing amyloid-β peptide and abnormally long poly-glutamine stretches. This mechanism modulates TGFβ signaling, enhances proteasome activity, and improves proteostasis within the ER. These effects are modulated by neuronal activity and by signaling originating from the reproductive system. These findings point to new research avenues for the development of proteostasis-promoting therapies for neurodegenerative maladies.
The protein homeostasis (proteostasis) network encompasses a myriad of mechanisms that maintain the integrity of the proteome by controlling various biological functions, including protein folding and degradation. Early in life, this network efficiently maintains the integrity of the proteome; however, as the organism ages, its competence declines. This decline enables the aggregation of certain proteins and, in some cases, underlies the development of late-onset neurodegenerative disorders, such as Alzheimer’s disease. Accordingly, maintaining proteostasis through the later stages of life holds the promise of harnessing the mechanisms that protect young organisms to delay the emergence of these devastating diseases. Thus, a comprehensive characterization of proteostasis regulators is needed to assess the feasibility of this approach. Recent findings nominate the nucleolus as an organelle that, among other organelles, coordinates proteostasis across tissues. We discovered that knocking down the activity of the nucleolar FIB-1–NOL-56 complex protects model nematodes from the proteotoxicity of the Alzheimer’s disease-causing amyloid-β peptide and abnormally long poly-glutamine stretches. This mechanism modulates TGFβ signaling, enhances proteasome activity, and improves proteostasis within the ER. These effects are modulated by neuronal activity and by signaling originating from the reproductive system. These findings point to new research avenues for the development of proteostasis-promoting therapies for neurodegenerative maladies.