**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Sofia Giorgetti, Department of Molecular Medicine, University of Pavia and Research Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

**Main Body of the Abstract**
β2 microglobulin (β2 m) is responsible for systemic human systemic amyloidosis either due to persistently high concentrations of the wild-type (WT) protein in hemodialyzed patients, or in the presence of mutations, such as D76N β2 m, which favor protein deposition in the adulthood, despite normal plasma levels.
Numerous studies have been carried out in vitroto characterize the mechanisms of β2 m amyloid conversion, however, many questions on the proteotoxicity in vivo are still open. Here we compare a Caenorhabditis elegans transgenic strain expressing human WT β2 m at high concentrations with the strain expressing the D76N β2 m variant at lower concentrations.
Both lines exhibit pathological phenotypes and show a significant remodeling of proteome and metabolome profiles, being more pronounced in the presence of higher levels of WT β2 m thus indicating that proteotoxicity correlates with β2 m levels rather than with the presence of mutations.
The β2 mexpression severely affects the nematode proteostasis inducing higher levels of molecular chaperones and other proteins involved in protein degradation. Redox imbalance and impairment in amino acids metabolism have also emerged. The joint proteomics and metabolomics pathway analysis highlights alterations in oxidative phosphorylation, fatty acids degradation and Krebs cycle, suggesting an impairment of the mitochondrial aerobic metabolism degradation and a shift to anaerobic metabolism.
Our studies confirm that the nematodes represent a good model suitable for studying the β2 m proteotoxicity in vivo. Most importantly, the “omics” approaches provide insightful clues at the molecular level unveiling specific deranged pathways.



**Author Listing - Lead/ Submitting Author (we will be communicating with this individual): Name, Institution, City and State where the work was done. Co-authors will be added in a separate section.**
Sofia Giorgetti, Department of Molecular Medicine, University of Pavia and Research Department, Fondazione IRCCS Policlinico San Matteo, Pavia, Italy

**Main Body of the Abstract**
β2 microglobulin (β2 m) is responsible for systemic human systemic amyloidosis either due to persistently high concentrations of the wild-type (WT) protein in hemodialyzed patients, or in the presence of mutations, such as D76N β2 m, which favor protein deposition in the adulthood, despite normal plasma levels.
Numerous studies have been carried out _in vitro_to characterize the mechanisms of β2 m amyloid conversion, however, many questions on the proteotoxicity _in vivo_ are still open. Here we compare a _Caenorhabditis elegans_ transgenic strain expressing human WT β2 m at high concentrations with the strain expressing the D76N β2 m variant at lower concentrations.
Both lines exhibit pathological phenotypes and show a significant remodeling of proteome and metabolome profiles, being more pronounced in the presence of higher levels of WT β2 m thus indicating that proteotoxicity correlates with β2 m levels rather than with the presence of mutations.
The β2 mexpression severely affects the nematode proteostasis inducing higher levels of molecular chaperones and other proteins involved in protein degradation. Redox imbalance and impairment in amino acids metabolism have also emerged. The joint proteomics and metabolomics pathway analysis highlights alterations in oxidative phosphorylation, fatty acids degradation and Krebs cycle, suggesting an impairment of the mitochondrial aerobic metabolism degradation and a shift to anaerobic metabolism.
Our studies confirm that the nematodes represent a good model suitable for studying the β2 m proteotoxicity _in vivo_. Most importantly, the “omics” approaches provide insightful clues at the molecular level unveiling specific deranged pathways.



Proteome and metabolome remodeling in C. elegans strains expressing different isoforms of human β2 microglobulin PC5 (#336)

We invite you to attend the XIX International Symposium on Amyloidosis to be held in Rochester, MN.

This symposium is organized as a hybrid meeting (with the focus on in-person) held from Sunday, May 26 through Thursday, May 30, 2024.

Together with the ISA Board and members of Mayo Clinic, a very attractive scientific hybrid program is being planned. The program will cover a variety of types of systemic amyloidosis: ATTR (hereditary and wild-type), AL (light-chain), AA and less frequent forms. There will be key lectures, specific symposia including those company sponsored, oral presentations and poster sessions of accepted abstracts.

COURSE DESCRIPTION
This program will provide a comprehensive review of state-of-the-art education in systemic amyloidosis: basic science, pathophysiology, diagnosis, current and emerging treatments. Scientific presentations will include competitive oral and poster abstracts. The rapid evolution of scientific discovery and expanding treatment options has created tremendous interest in the field and this meeting will fill and important gap in educating scientists and clinicians.