Related Experiment Video
Updated: Jun 4, 2025

Molecular Modulation by Lentivirus-Delivered Specific shRNAs in Endoplasmic Reticulum Stressed Neurons
Published on: April 24, 2021
A nucleolar mechanism suppresses organismal proteostasis by modulating TGFβ/ERK signalling
Huadong Zhu1, Reut Bruck-Haimson1, Adam Zaretsky1
1Department of Biochemistry and Molecular Biology, the Institute for Medical Research Israel-Canada, the Faculty of Medicine, The Hebrew University of Jerusalem, Jerusalem, Israel.
Abstract:
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. Alas, ageing-associated decline in the efficiency of this network enables protein aggregation and consequently the development of late-onset neurodegenerative disorders, such as Alzheimer's disease. Accordingly, the maintenance of proteostasis through late stages of life bears the promise to delay the emergence of these devastating diseases. Yet the identification of proteostasis regulators is needed to assess the feasibility of this approach. Here we report that knocking down the activity of the nucleolar FIB-1-NOL-56 complex protects model nematodes from proteotoxicity of the Alzheimer's disease-causing amyloid-β peptide and of abnormally long poly-glutamine stretches. This mechanism promotes proteostasis across tissues by modulating the activity of TGFβ signalling and by enhancing proteasome activity. Our findings point at research avenues towards the development of proteostasis-promoting therapies for neurodegenerative maladies.
Related Concept Videos
TGF - β Signaling Pathway
Regulation of Nuclear Protein Sorting
The Unfolded Protein Response
Receptor Downregulation in MVBs
The EGFR can initiate signaling pathways that lead to cell proliferation, migration, and differentiation. Overexpression of EGFR stimulates cells to proliferate. Excessive EGFR...
NF-κB-dependent Signaling Pathway
NF-κB-dependent Signaling Mechanism
The...
Abnormal Proliferation

