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Updated: May 15, 2026
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Methods to Study Changes in Inherent Protein Aggregation with Age in Caenorhabditis elegans
Published on: November 26, 2017
A novel interaction between aging and ER overload in a protein conformational dementia
Angela Schipanski1, Sascha Lange, Alexandra Segref
1Institute of Neuropathology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
Genetics
|January 22, 2013
Summary
Familial encephalopathy with neuroserpin inclusion bodies (FENIB) involves protein aggregation. Impaired protein homeostasis and altered unfolded protein response (UPR) pathways exacerbate neuroserpin accumulation, suggesting UPR capacity as a therapeutic target.
Area of Science:
- Neuroscience
- Molecular Biology
- Genetics
Background:
- Intraneuronal protein aggregation, seen in tauopathies and Parkinson disease, impairs protein homeostasis.
- Familial encephalopathy with neuroserpin inclusion bodies (FENIB) is a conformational dementia caused by mutant neuroserpin polymerization.
- The relationship between neuronal proteostasis and protein aggregation kinetics is not well understood.
Purpose of the Study:
- To investigate the dynamics of aggregate formation in familial encephalopathy with neuroserpin inclusion bodies (FENIB).
- To explore the link between protein homeostasis and neuroserpin aggregation in vivo.
- To identify conserved pathways modulating protein aggregation.
Main Methods:
- Studied FENIB in Caenorhabditis elegans and mice models.
- Investigated the aggregation of neuroserpin homolog SRP-2 in worms.
- Analyzed the role of unfolded protein response (UPR) and heat shock response pathways.
Main Results:
- Mutant neuroserpin homolog SRP-2 aggregated in the ER lumen in worms, mimicking human FENIB.
- Downregulation of UPR pathways in worms increased mutant SRP-2 accumulation.
- Mice overexpressing mutant neuroserpin showed transient UPR induction, with age-related UPR induction linked to polymer accumulation.
- Proteostasis perturbations, including impaired heat shock response or altered UPR signaling, enhance neuroserpin accumulation.
Conclusions:
- Proteostasis and UPR signaling are critical in modulating neuroserpin aggregation.
- Age-related ER overload and UPR induction suggest a novel interaction.
- Enhancing neuronal UPR capacity presents a potential therapeutic strategy for FENIB and related disorders.
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