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Ka Ying Connie Fung - Investigating the hepatic processing of the Z-variant of alpha-1-antitrypsin in a zebrafish model (final).pdf (10.36 MB)

Investigating the hepatic processing of the Z-variant of alpha-1-antitrypsin in a zebrafish model

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posted on 2022-09-06, 05:52 authored by KA YING CONNIE FUNG
The Z variant of alpha-1-antitrypsin (ZAAT) is associated with severe antitrypsin deficiency. Retention of ZAAT in the liver predispose individuals to develop liver disease, and limit its secretion into the circulation. A zebrafish model expressing ZAAT displays serum insufficiency but no liver accumulation, suggesting efficient mechanisms in the zebrafish liver to clear misfolded ZAAT. Collectively, our results suggest the processing of ZAAT by protein degradation machinery in hepatocytes lead to cholesterol homeostasis perturbation. Furthermore, the removal of a stress response factor enhances ZAAT secretion, thus providing a novel therapeutic strategy for treating antitrypsin deficiency.

History

Principal supervisor

Phillip Ian Bird

Additional supervisor 1

Robert Bryson-Richardson

Year of Award

2022

Department, School or Centre

Biomedical Sciences (Monash Biomedicine Discovery Institute)

Additional Institution or Organisation

Biochemistry and Molecular Biology

Campus location

Australia

Course

Doctor of Philosophy

Degree Type

DOCTORATE

Faculty

Faculty of Medicine, Nursing and Health Sciences

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    Faculty of Medicine, Nursing and Health Sciences Theses

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